Search

Concerns around concussion highlight the need for strategies to improve the implementation and translation of concussion guidelines in community sports. This study assessed players' utilisation and compliance with New Zealand Rugby's Concussion Management Pathway (CMP). This pragmatic, mixed methods study comprised of concussion injury surveillance and mapping of players' healthcare touchpoints through the CMP. Semi-structured interviews were conducted to understand stakeholders' experiences. Over the season, 27 different healthcare pathways were identified with 28% of players progressing through all phases of the CMP (ideal pathway). Of the 206 suspected concussions reported over the season, 70% were logged in the CMP phone App, and 89% of these had an associated valid baseline concussion assessment. Prior to returning to contact training, 64% of players obtained a medical clearance. One theme, 'belief in the value of pathway' was identified as a facilitator across all CMP components. Themes such as 'concussion knowledge and the nature of concussion'; 'communication between stakeholders and sufficient information on the process'; and 'strong relationships and clarity around responsibilities' were identified as facilitators across several pathway components. Other facilitators included 'ease and timing of general practitioner access'; 'the phone App as facilitator to logging'; and 'spotting for concussion as a team'. Additionally, the findings signify baseline testing as a potential pre-cursor to overall CMP compliance. Strategies that support the facilitators identified in this study may further enhance compliance., (© 2024 The Author(s). European Journal of Sport Science published by Wiley‐VCH GmbH on behalf of European College of Sport Science.)

Objective: To examine the likelihood of head acceleration events (HAEs) as a function of previously identified risk factors: match time, player status (starter or substitute) and pitch location in elite-level men's and women's rugby union matches., Methods: Instrumented mouthguard data were collected from 179 and 107 players in the men's and women's games and synchronised to video-coded match footage. Head peak resultant linear acceleration (PLA) and peak resultant angular acceleration were extracted from each HAE. Field location was determined for HAEs linked to a tackle, carry or ruck. HAE incidence was calculated per player hour across PLA recording thresholds with 95% CIs estimated. Propensity was calculated as the percentage of contact events that caused HAEs across PLA recording thresholds, with a 95% CI estimated. Significance was assessed by non-overlapping 95% CIs., Results: 29 099 and 6277 HAEs were collected from 1214 and 577 player-matches in the men's and women's games. No significant differences in match quarter HAE incidence or propensity were found. Substitutes had higher HAE incidence than starters at lower PLA recording thresholds for men but similar HAE propensity. HAEs were more likely to occur in field locations with high contact event occurrence., Conclusion: Strategies to reduce HAE incidence need not consider match time or status as a substitute or starter as HAE rates are similar throughout matches, without differences in propensity between starters and substitutes. HAE incidence is proportional to contact frequency, and strategies that reduce either frequency or propensity for contact to cause head contact may be explored., Competing Interests: GT and BJ have received research funding from Prevent Biometrics and World Rugby. KAS and MB have received research funding from World Rugby. LS, RT, ECF, DMS and JB are employed by or contracted as consultants to World Rugby. GT previously conducted consultancy work for World Rugby. KAS and SPTK are employed by the Rugby Football Union. SH receives funding for his PhD studies from the Rugby Football Union and Premiership Rugby. BJ is a consultant with Premiership Rugby and the Rugby Football League. MC is employed by Premiership Rugby and was previously employed by the Rugby Football Union. PO'H has previously been contracted by the Rugby Football Union and is employed by Marker Diagnostics UK, a company developing salivary biomarker testing for sport-related concussion., (Copyright © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To examine the propensity of tackle height and the number of tacklers that result in head acceleration events (HAEs) in elite-level male and female rugby tackles., Methods: Instrumented mouthguard data were collected from women (n=67) and men (n=72) elite-level rugby players from five elite and three international teams. Peak linear acceleration and peak angular acceleration were extracted from HAEs. Propensities for HAEs at a range of thresholds were calculated as the proportion of tackles/carries that resulted in an HAE exceeding a given magnitude for coded tackle height (low, medium, high) and number of tacklers. Propensity ratios with 95% CIs were calculated for tackle heights and number of tacklers., Results: High tackles had a 32.7 (95% CI=6.89 to 155.02) and 41.2 (95% CI=9.22 to 184.58) propensity ratio to cause ball carrier HAEs>30 g compared with medium tackles for men and women, respectively. Low tackles had a 2.6 (95% CI=1.91 to 3.42) and 5.3 (95% CI=3.28 to 8.53) propensity ratio to cause tackler HAEs>30 g compared with medium tackles for men and women, respectively. In men, multiple tacklers had a higher propensity ratio (6.1; 95% CI=3.71 to 9.93) than singular tacklers to cause ball carrier HAEs>30 g but a lower propensity ratio (0.4; 95% CI=0.29 to 0.56) to cause tackler HAEs>30 g. No significant differences were observed in female tacklers or carriers for singular or multiple tacklers., Conclusion: To limit HAE exposure, rule changes and coaching interventions that promote tacklers aiming for the torso (medium tackle) could be explored, along with changes to multiple tackler events in the male game., Competing Interests: GT has received research funding from World Rugby and Prevent Biometrics and has previously conducted consultancy work for World Rugby. LS, RT, ÉCF and DMS are employed by or contracted as consultants for World Rugby., (Copyright © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: New Zealand Rugby (NZR) implemented a concussion management pathway (CMP) to improve management at the community level. Physiotherapists play an important role in the CMP., Objective: This study explored physiotherapists' experiences in the management of community rugby-related concussion as part of the CMP., Methods: We adopted a pragmatic, descriptive qualitative approach to explore perceptions of twenty-four physiotherapists involved in the CMP. Thematic analysis was used to analyze data., Results: Four themes represented participants' experiences: 1) 'walking the tight rope between player welfare and performance' described the balancing act between different attitudes and priorities of the various rugby stakeholders; 2) empowering physiotherapists' authority and responsibilities, described the influence of physiotherapists' authority within the team and concussion management responsibilities; 3) multi-directional communication, described the role of communication between multiple stakeholders; and 4) the influence of context, which included the complexity of concussion, concussion knowledge of the physiotherapists and team, resource support for the physiotherapist, and access to a medical doctor., Conclusion: Physiotherapists had positive attitudes toward the CMP and are well-positioned to play an active role in the pathway. Priorities of other stakeholders, authority of the physiotherapist and the communication flow influences physiotherapists' ability to optimally manage players with concussion.

Context: Few studies utilize randomized clinical trials (RCT) to quantify clinical intervention safety of rehabilitation after sport-related concussion across sport levels., Objective: Describe symptom exacerbation and adverse events (AEs) associated with two concussion rehabilitation interventions., Design: Cluster Randomized Controlled Trial (XXX)., Setting: Sports medicine clinic and field settings., Participants: The RCT enrolled 251 concussed athletes (median age=20 years; female n=48) across 28 sites from New Zealand professional rugby (n=31), Canadian professional football (n=52), United States (U.S.)/Canadian colleges (n=128) and U.S. high schools (n=40)., Interventions: Two medically supervised interventions: 1) Enhanced Graded Exertion (EGE): international return to sport strategy and sport specific activities only (EGE-only n=119) and 2) Multidimensional Rehabilitation (MDR) followed by EGE: early symptom-directed exercises once symptoms were stable, followed by EGE after symptoms resolved (MDR+EGE n=132)., Main Outcome Measures: Primary outcomes were intrasession total symptom severity score exacerbation and significant intersession (increase 10+ severity points) sustained total symptom severity exacerbation, each measured with a Postconcussion Symptom Scale (132 total severity points on scale). Reported AEs were also described. Activity-based rehabilitation sessions (n=1437) were the primary analysis unit. Frequencies, proportions, medians, and Interquartile Ranges (IQRs) were calculated for outcomes by treatment group., Results: The 251 post-injury participants completed 1437 (MDR+EGE=819, EGE-only=618) activity-based intervention sessions. A total of 110 and 105 participants contributed data (those missing had no documented session data) to at least 1 activity-based session in the MDR+EGE and EGE-only arms respectively. Intrasession symptom exacerbations were equivilantly low in MDR+EGE and EGE-only arms (MDR+EGE: 16.7%, 95% CI:14.1%,19.1%; EGE-only: 15.7%, 95% CI: 12.8%,18.6%). In total, 9/819 MDR+EGE sessions (0.9%) and 1/618 EGE-only sessions (0.2%) resulted in a pre- to post-session symptom exacerbation beyond a 10+ severity point increase; 8/9 resolved to <10 points by the next session. Two study-related AEs (1 in each arm) were reported., Conclusions: Participants in MDR+EGE and EGE-only activities reported equivalently low rates of symptom exacerbation.

There is a growing concern around concussions in rugby union, at all levels of the game. These concerns highlight the need to better manage and care for players. However, consistency around concussion-related responsibilities of stakeholders across the community rugby system remains challenging. Taking a systems thinking approach, this pragmatic, qualitative descriptive study explored key stakeholder groups within New Zealand's community rugby system's perceptions of their own and others' concussion-related responsibilities. Participants included players from schools and clubs, coaches, parents, team leads and representatives from four provincial unions. A total of 155 participants (67 females and 88 males) were included in the study. Focus groups and individual interviews were conducted. Thematic content analysis was used to analyse data. Thirty concussion-related responsibilities were identified. These responsibilities were contained within four themes: (1) policies and support (responsibilities which influence policy, infrastructure, human or financial resources); (2) rugby culture and general management (responsibilities impacting players' welfare and safety, attitudes and behaviour, including education, injury reporting and communication); (3) individual capabilities (responsibilities demonstrating knowledge and confidence managing concussion, leadership or role/task shifting) and (4) intervention following a suspected concussion (immediate responsibilities as a consequence of a suspected concussion). The need for role clarity was a prominent finding across themes. Additionally, injury management initiatives should prioritise communication between stakeholders and consider task-shifting opportunities for stakeholders with multiple responsibilities. How concussions will realistically be managed in a real-world sports setting and by whom needs to be clearly defined and accepted by each stakeholder group. A 'framework of responsibilities' may act as a starting point for discussion within different individual community rugby contexts on how these responsibilities translate to their context and how these responsibilities can be approached and assigned among available stakeholders., Competing Interests: Competing interests: During the course of the study, DMS and JC were employed by NZ Rugby., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

New Zealand Rugby (NZR) implemented a concussion management pathway (CMP), aimed at improving management at community level. General Practitioners (GPs) played a large role in the design of this process. The objective of this study was to explore GPs' perceptions of barriers and facilitators of the CMP and rugby-related concussion management in the community. A descriptive qualitative approach using interviews and focus groups was employed. Four themes were derived: i) GPs' existing knowledge and confidence around concussion management; ii) Operational resources: time, remuneration and pathway guidance; iii) Standardising concussion care and iv) Expanding the circle of care - the need for multi-disciplinary healthcare team. These themes described how GP's concussion knowledge, and the efficiency and availability of operational resources affected their experience and ability to fulfil their tasks within the CMP. GPs found NZR's CMP especially valuable, as it provided guidance and structure. Expanding the role of other healthcare providers was seen as critical to reduce the burden on GPs, while also delivering a more holistic experience to improve clinical outcomes. Addressing the identified barriers and expanding the network of care will help to improve the ongoing development of NZR's CMP, while supporting continued engagement with all stakeholders.

Primary Objective: To describe the collaborative development of a New Zealand Rugby Concussion Assessment (NZRCA) for primary care and to provide normative baseline data from a representative group of high school rugby players., Methods: This study, conducted over the 2018 and 2019 community rugby season where players were baseline tested during the pre- or start of season period., Results: Data were collected from 1428 players (males n = 1121, females n = 307) with a mean age of 15.9 ± 1.4 years. The mean ± SD symptom severity score was 11.3 ± 8.6, the mean number of endorsed symptoms was 8.5 ± 5.3 and the percentage feeling "normal" was 80.2 ± 15.3%. Only 5.3% of players reported no symptoms at baseline. The most common reported were: 'distracted easily' (72.5%), 'forgetful' (68.5%), and 'often tired' (62.6%). None of the participants achieved a perfect score for the SAC50. The majority of participants (89.7%) passed the tandem gait test with a time of 12.2 ± 1.7 seconds. Age, gender, and ethnicity were associated with NZRCA performance; albeit weakly., Conclusion: This study provides normative reference values for high-school rugby players. These data will aid healthcare providers in their identification of suspected concussion in the absence of individualized baselines.

Objective: To report pre-season baseline concussion assessment performance among senior rugby players and explore associations between assessment performance and player demographics., Design: A cross-sectional study using the New Zealand Rugby Concussion Assessments (NZRCA), comprising symptom, cognitive and dynamic coordination assessments was conducted in the 2018-2019 season., Methods: Players' baseline assessments were characterised using descriptive statistics; effect sizes (ES) and t-tests were used to explore associations between player demographic characteristics and NZRCA performance., Results: A total of 733 players (11.4% female) aged between 16 and 52 years completed the NZRCA. The median (range) value for symptom severity, endorsed symptoms and "percentage normal" was respectively, 5 (0-40), 5 (0-21) and 90% (30-100%). A perfect standardised assessment of concussion score was achieved by one participant; seven achieved ≥27/30 for immediate recall, and 22 achieved a perfect delayed recall score. Most participants (n = 674, 92%) passed the tandem gait test. Associations between NZRCA performance and gender, concussion history, and Pasifika ethnicity were observed with effect sizes ranging from small (0.18) to large (0.70). Six hundred and twenty-three (85%) participants reported at least one symptom., Conclusions: The results from this study could help support decision-making by clinicians, improving the management of concussions in the community setting.

In rugby union concussions are a player welfare concern, particularly in the community game where there is often minimal sideline medical support. New Zealand Rugby (NZR) has three primary goals around the management of concussions in the community game: (1) players with a suspected concussion are removed from the game or training; (2) players are referred into primary care for a diagnosis by a general practitioner(GPs) (doctor in primary care); (3) prior to returning to contact training that they are medically cleared by a doctor. Given their role in the diagnosis and medical clearance of players with a concussion, GPs are a key stakeholder in the concussion management pathway. Thus to ensure that players are safely returning to play, NZR acknowledged the need to better support and engage with GPs. This editorial is an opportunity for NZR to share our experience working collaboratively with GPs in New Zealand to support the diagnosis and medical clearance of players following a rugby-related concussion.

The purpose of this study was to survey high school rugby players from a range of ethnic, geographic and socioeconomic backgrounds in New Zealand (NZ) to gain an understanding of concussion knowledge, awareness of NZ Rugby's (NZR) guidelines and attitudes towards reporting behaviours. Male and female high school rugby players (n= 416) from across NZ were surveyed. The findings indicated that 69% of players had sustained a suspected concussion, and 31% had received a medical diagnosis of concussion. 63% of players indicated they were aware of NZR's guidelines. Māori and Pasifika players were less likely to be aware of the guidelines compared to NZ European, Adjusted OR 0.5, p = 0.03. Guideline awareness was significantly higher for those from high decile schools when compared to low (Unadjusted OR 1.63, p = 0.04); however, when ethnicity and school locations were controlled for this became non-significant (Adjusted OR= 1.3, p=0.37). The coach was the key individual for the provision of concussion information and disclosure of symptoms for players. The findings of this study will inform the development and delivery of NZR's community concussion initiative and how these examined factors influence a high school player's concussion knowledge and reporting behaviour.

Salmon, DM, Handcock, PJ, Sullivan, SJ, Rehrer, NJ, and Niven, BE. Can neck strength be measured using a single maximal contraction in a simulated contact position? J Strength Cond Res 32(8): 2166-2173, 2018-Neck strengthening has been postulated to potentially reduce the incidence and severity of concussions and neck injuries in collision-based sports. A quick and reliable method to assess neck strength would permit identification of those at risk and tracking of progress after injury. The purpose of this study was to determine if neck strength could be reliably assessed in a simulated contact posture using a single maximal contraction. During a single session, 30 healthy male university students performed 3 maximal voluntary contractions of the neck musculature in each of the following directions: extension (Ext), flexion (Flx), left lateral flexion (LtFlx), and right lateral flexion (RtFlx). To evaluate the reliability of these measures, intraclass correlation coefficients (ICCs) were calculated. The findings revealed a significant effect for direction (p < 0.01), where Ext (234.8 N) tested stronger than Flx (141.0 N), LtFlx (134.5 N), and RtFlx (123.0 N). In addition, Flx tested stronger than RtFlx (p = 0.03). No other differences were observed between LtFlx and RtFlx. When the combined mean values of the trials (1: 151.6 N, 2: 160.0 N, 3: 163.5 N) and the interaction contrast were compared, these were not significant (p = 0.08-1.0), indicating no changes in peak force occurred over the 3 trials. The ICC values for Ext, RtFlx, and LtFlx were all "excellent" (0.91-0.94), whereas Flx demonstrated "good" reliability (0.86). In a simulated contact posture, a reliable measure of peak force was obtained using a single maximal contraction. This may have practical applications for the quick and reliable assessment of contact sport athletes in a position that has functional relevance to their sports.

Background: Neck strength has been reported to reduce the incidence of concussions and neck injuries. However, little is known about how neck strength changes over a playing season. The aim of this study was to understand the impact a 20-week rugby season has on neck strength, neck pain (NP) and neck stiffness (NS) in a cohort of rugby players, relative to a non-contact control group., Methods: This prospective cohort study employed a fixed-frame dynamometer to measure neck strength in a simulated contact posture in rugby players (N.=32) and controls (N.=15). During each assessment, participants performed a single maximal voluntary contraction in extension, flexion, left (LtFlx) and right lateral flexion (RtFlx). To quantify neck dysfunction, "current," "average," and "worst" NP and NS were measured using visual analogue scales., Results: Post-season improvements (35.3-59.1 N) in neck strength were observed for the forwards for all measured directions (P<0.01), and were significant when compared to controls. For the backs, improvements were seen in extension, flexion and LtFlx (P=0.01-0.05), with only extension (29.8 N) and flexion (35.14 N) remaining significant when contrasted against the controls. The controls' neck strength remained unchanged over the season. Despite improvements in peak force, NP increased (all three measures) for the forwards (P=0.01-0.04), while only current (P=0.03) and worst NP (P=0.04) increased for the backs. Unexpectedly, NS remained unchanged for the forwards, while backs reported increases for all three measures (P=0.01-0.02)., Conclusions: A season of rugby resulted in neck strength adaptations in the rugby players. Despite these improvements, increased levels of NP and NS were reported.

Previous research demonstrated higher maximal voluntary contraction (MVC) force with upright vs. inverted positions in untrained individuals. The purpose was to determine the effects of inversion on force, activation, and cardiovascular responses before and following fatigue in trained individuals. Twelve male athletes completed two trials: upright and inverted seated positions. At baseline (upright), either leg extension (LE) or elbow flexion (EF) evoked contractile properties and MVCs were performed. LE and EF contractions were randomly allocated and performed in separate sessions. The subject was then positioned for 150s in each posture, followed by a 30s MVC (MVC30). During each trial, stroke volume (SV), cardiac output (Q), heart rate (HR), time and frequency domain HR variability measures and mean arterial blood pressure (MAP) measurements were recorded. ANOVA showed no statistical differences in EF MVC force, but a tendency (p=.12) for LE MVC decline with inversion vs. upright. Evoked resting (p=.1) and potentiated peak twitch (p=.04) force were increased with inverted LE but tended to diminish with inverted EF (p=.06 and p=.1). Force-fatigue, electromyography-fatigue relationships and HR variability during MVC30 fatigue were not affected. HR and Q were significantly (p=.01) lower with inversion following both LE and EF fatigue. Compared to the significant inversion-induced changes associated with untrained individuals in previously published studies, the lack of postural changes in resting force and CV measures may demonstrate that highly trained individuals adapt better to inversion., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The purpose of this study was to examine the reliability of repeated isometric measurements of neck strength and endurance in a simulated rugby contact posture. Data were collected from healthy active university students (n = 20) over 3 sessions. Each session consisted of a single maximal voluntary contraction (MVC) and endurance trial for extension and flexion. The endurance trials were analyzed to determine the area under the force curve (%AUC) and the time to fatigue (TTF). Reliability was calculated using the SEM and minimal detectable change (MDC). The results revealed that the MVC values for extension were nonsignificant for session (p = 0.21), whereas some session differences were seen for flexion (p = 0.01), where session 1, 115.3 N was less than session 3, 126.4 N (p = 0.03). For %AUC, flexion values (%AUC 86.0) were greater than extension (%AUC 59.4) (p = 0.02). A similar effect was observed for TTF with flexion (125.0 seconds) having significantly greater TTF than extension (86.1 seconds). For peak force, the greatest SEM and MDC were achieved for extension (15.3 and 42.3 N), while flexion produced lower values (11.3 and 31.2 N). In contrast, for the endurance trials, SEM and MDC were greater in flexion than in extension. The findings from this study indicate that the neck musculature can be reliably assessed in a simulated contact posture. For peak force, extension provided more consistent measures across time as there seems to be a learning effect for flexion. Additionally, the SEM and MDC scores provide a useful tool for future assessment of neck strength and endurance.

Introduction: To address the high prevalence of neck dysfunction in helicopter aircrew, a 12-wk training program was designed to examine the effects on neck muscular strength and endurance., Methods: Subjects were recruited from Canadian Forces (CF) helicopter aircrew and randomized into either a neck coordination training program (CTP; N = 10), an endurance training program (ETP; N = 11), or a nontreatment control (CON; N = 8). Baseline assessments determined maximal voluntary contraction (MVC) strength and endurance capacity using a submaximal contraction to fatigue at 70% of their MVC for extension, flexion, and left (Ltflx) and right (Rtflx) lateral flexion. The ETP subjects performed dynamic contractions at 30% of their MVC in the four testing directions using a head harness and Thera-band tubing. The CTP consisted of exercises that focused on strengthening the deep cervical musculature using the mass of the head as resistance and progressing to exercises that incorporated the superficial cervical muscles., Results: Post-intervention, the ETP achieved the only statistically significant increase in maximal force when compared to the CON (14.4%). Improved times to fatigue were achieved by the CTP for flexion (26.34 +/- 20.72 s), Ltflx (23.54 +/- 13.94 s), and Rtflx (28.72 +/- 4.88 s)., Conclusion: The provision of an ETP and CTP resulted in a positive trend toward improved maximal force and muscular endurance. The greatest improvements in endurance and strength were found for those subjects assigned to the CTP treatment. Our research demonstrates the importance of including a designed and supervised training program into the daily routine of helicopter aviators.

Neck pain is a growing aeromedical concern for military forces on an international scale. Neck pain prevalence in the global military helicopter community has been reported in the range of 56.6-84.5%. Despite this high prevalence, historically, research examining helicopter aircrews has focused predominantly on low back pain. A number of recent studies have emerged examining flight-related factors that are hypothesized to contribute to the development of flight-related neck pain. Loading factors such as the posture adopted during flight, use of night vision goggles, and vibration have all been found to contribute to neck pain and muscular fatigue. Prolonged or repeated exposureto these loading factors has been hypothesized to perpetuate or contribute to the development of neck pain. Despite the high number of helicopter aircrew personnel that suffer from neck pain, very few individuals seek treatment for the disorder. The focus of medical personnel should, therefore, be directed toward a solution that addresses not only the issue of muscular fatigue, but the hesitancy to seek treatment. Previous research in military and civilian populations have used exercise therapy as a treatment modality for neck pain and have found improved endurance capacity in the neck musculature and reduced self-reported neck pain.

The possible applications of the measurement of platelet aggregation by conventional photometry are limited by the short lifetime of platelet suspensions. Recently a microplate-based technique was introduced, which promised to revolutionize experimental design by enabling simultaneous assessment of 96 platelet samples. However, adoption of this technique has been slow since the available equipment was not able to satisfy all the conditions required for conventional aggregometry, especially adequate agitation of samples whilst maintaining total control of incubation temperature. This report describes how these problems may be overcome, together with the introduction of on-line analysis of data using commercially available software, obviating the complexities of data management previously encountered.

Isolated adrenal fasciculata cells were purified by centrifugation through a 0-50% hyperbolic gradient of PercollR. The dose-dependence and kinetics of both intracellular cyclic AMP accumulation and steroidogenesis in response to ACTH1-39 and ACTH5-24 (corticotropin-(1-39) and corticotropin-(5-24)-peptides) were determined using purified cells. The rate of intracellular cyclic AMP formation was maximal during the first five minutes after hormone addition and remained constant or fell thereafter. Therefore intracellular cyclic AMP accumulation, assessed after 5 min., was compared with steroid output after 20 min. Maximal steroidogenesis was elicited by ACTH5-24 without discerning a significant stimulation of intracellular cyclic AMP accumulation. ACTH6-24 (corticotropin-(6-24)-peptide) could completely inhibit the intracellular cyclic AMP accumulation elicited by ACTH1-39 or by ACTH5-24 at concentrations that only partially inhibited steroidogenesis. It is possible that there are two pathways for the steroidogenic action of ACTH, one of which is obligatorily mediated by intracellular cyclic AMP, and another which involves a different mediator.

Time- and dose-dependent changes in intracellular enzyme activities in kidney and bone from rats injected with calcitonin have been assessed by quantitative cytochemistry. The doses of salmon calcitonin given were similar to those suggested in the Pharmacopoeial rat hypocalcaemia bioassay (1-50 mIU/50 g body weight). The highest doses produced 30% inhibition of alkaline phosphatase activity, maximal within 20 min after injection, in cells of renal proximal tubules and a stimulation of calcium-dependent adenosine triphosphatase activity in kidney cortical and outer medullary cells. Alkaline phosphatase activity in the periosteal bone cells was markedly inhibited at the lowest doses. When doses of human and porcine calcitonins were given which would be equipotent with that of salmon calcitonin in the rat hypocalcaemia bioassay, the effect of the non-mammalian peptide on renal alkaline phosphatase activity was relatively greater than that of the mammalian peptides. Oxidized human calcitonin did not inhibit renal alkaline phosphatase activity even when an amount equivalent to 10 times the highest dose of the unmodified peptide was injected.

Graded increments in the fat-to-carbohydrate ratio of the diet elicited a gradual, but reversible increase in the average mass of body fat maintained by adult female (CDI) albino mice under ad libitum feeding conditions. In addition, the inter-individual variability in the animals' fat mass was greatly magnified by diets with a substantial fat content (greater than 30 percent of calories). As a result, the incidence of obesity (defined as one third or more of body weight as fat) increased progressively from 0 percent to 35 percent when the diet's fat content was varied from 1 percent to 64 percent of its total energy content. A state of weight maintenance can only become established when the relative rates of glucose and fatty acid oxidation are proportional, on average, to the carbohydrate-to-fat ratio of the diet. When diets with a relatively high fat content are consumed, a considerable enlargement of the adipose tissue mass appears to be necessary in many animals before weight maintenance becomes spontaneously established. It is proposed, therefore, that changes in the adipose tissue mass, along with shifts in the range in which glycogen levels are maintained, and other adaptive changes, contribute to bring about rates of fat oxidation commensurate with a diet's fat content. This impact of dietary composition on body composition may be a factor contributing to the increased incidence of obesity in affluent populations consuming diets with a substantial fat content.

In single smooth muscle cells held at depolarized potentials under voltage-clamp, spontaneous transient outward currents (STOCs) of about 100 ms in duration and 100-300 pA in size are observed. These behave as if they are caused by the cyclical release of calcium from storage sites within the cell and can therefore be used as a method of monitoring the release of calcium from these stores by various agents. Muscarinic receptor activation or caffeine applied to single smooth muscle cells from rabbit jejunum produced outward current, probably due to the release of calcium from stores, and STOCs were subsequently abolished. Levels of inositol 1,4,5 trisphosphate in fragments of the muscle were increased within 5 s by carbachol application. STOCs and outward current due to calcium store release were probably due to the opening of calcium-activated K-channels since they were abolished by 4 mM tetraethylammonium. Receptor activation also opens channels that admit cations, including calcium, which may also contribute to tension generation.

In longitudinal smooth muscle from guinea-pig intestine prelabelled with [3H]inositol, carbachol produced a 3-fold increase in [3H]inositol 1,4,5-trisphosphate within 2 s, and there was also a simultaneous increase in [3H]inositol 1,4-bisphosphate. 3H-labelling of inositol 1,3,4,5-tetrakisphosphate was not significantly increased until 60 s after carbachol stimulation, and the accumulation of [3H]inositol 1,3,4-trisphosphate was relatively small.

1. Fatty acid synthesis de novo was measured in the perfused liver of fed mice. 2. The total rate, measured by the incorporation into fatty acid of (3)H from (3)H(2)O (1-7mumol of fatty acid/h per g of fresh liver), resembled the rate found in the liver of intact mice. 3. Perfusions with l-[U-(14)C]lactic acid and [U-(14)C]glucose showed that circulating glucose at concentrations less than about 17mm was not a major carbon source for newly synthesized fatty acid, whereas lactate (10mm) markedly stimulated fatty acid synthesis, and contributed extensive carbon to lipogenesis. 4. The identification of 50% of the carbon converted into newly synthesized fatty acid lends further credibility to the use of (3)H(2)O to measure hepatic fatty acid synthesis. 5. The total rate of fatty acid synthesis, and the contribution of glucose carbon to lipogenesis, were directly proportional to the initial hepatic glycogen concentration. 6. The proportion of total newly synthesized lipid that was released into the perfusion medium was 12-16%. 7. The major products of lipogenesis were saturated fatty acids in triglyceride and phospholipid. 8. The rate of cholesterol synthesis, also measured with (3)H(2)O, expressed as acetyl residues consumed, was about one-fourth of the basal rate of fatty acid synthesis. 9. These results are discussed in terms of the carbon sources of hepatic newly synthesized fatty acids, and the effect of glucose, glycogen and lactate in stimulating lipogenesis, independently of their role as precursors.

The incorporation of 32P from [gamma-32P]ATP into intracellular proteins was studied in electrically permeabilized rat islets of Langerhans. Ca2+ (10 microM), cyclic AMP (100 microM) and a protein kinase C-activating phorbol ester, phorbol 13-myristate 12-acetate (PMA; 100 nM) produced marked changes in the phosphorylation state of a number of proteins in permeabilized islets after incubation for 1 min at 37 degrees C. Ca2+ modified the effects of cyclic AMP and PMA on protein phosphorylation. Noradrenaline (10 microM) had no detectable effects on Ca2+-dependent protein phosphorylation, but significantly inhibited Ca2+-induced insulin secretion from electrically permeabilized islets. These results suggest that electrically permeabilized islets offer a useful model in which to study rapid events in protein phosphorylation as a mechanism of stimulus-secretion coupling. If the rapid Ca2+-induced effects on protein phosphorylation are involved in the control of insulin secretion, the results of this study also imply that part of the catecholamine inhibition of insulin secretion occurs at a stage in the secretory pathway beyond the activation of the regulated protein kinases.

To test the hypothesis that phosphatidic acid (PhA) is involved in the carbachol inhibition of hormone stimulated accumulation of cAMP we observed the effects of PhA on PGE1-stimulation of cAMP in WI-38 fibroblasts. PhA inhibited PGE1-stimulated cAMP accumulation of WI-38 fibroblasts; maximum inhibition (approximately 50-80%) occurred at a PhA concentration of 1.0 microM and significant inhibition was observed with a concentration of 0.1 microM. The full effects of PhA were evident within 15 sec after the co-addition of PGE1 and PhA. Addition of PhA to cells which had been pre-stimulated with PGE1 resulted in the rapid decay of cAMP levels to a new steady state level with a t 1/2 of approximately 65 sec. The inhibition produced by PhA did not appear to be simply attributable to a depolarization or increased intracellular Ca2+, since addition of either KCl or the Ca2+ ionophore A23187 did not lower PGE1-stimulated cAMP accumulation. When intact cells were pretreated with PhA then lysed and adenylate cyclase immediately assayed, no detectable changes in broken cell adenylate cyclase activities were observed. Also, PhA added directly to adenylate cyclase assays at concentrations as high as 100 microM produced no detectable inhibition of the membrane fraction adenylate cyclase activities. Nonetheless, our results suggest that adenylate cyclase activity in intact cells may be directly affected by physiological levels of PhA . Further, the similarities of carbachol [Butcher, R. W., Journal of Cyclic Nucleotide Research, 4:411 (1978)] and PhA inhibition support the hypothesis that carbachol (acetylcholine) exerts its effect on adenylate cyclase through alterations of the plasma membrane phospholipid composition.

Growing rats were treated with daily im doses of salmon calcitonin (sCT) (2, 15 and 100 IU/kg) for various times (1, 4 and 24 weeks). The effects on intracellular enzyme activities in bone and kidney were monitored using quantitative cytochemical methods previously developed for the identification of specific target tissue responses to calcitonins. The basal alkaline phosphatase activities in both kidney and bone were decreased by long-term treatment at all time periods and doses tested. No change was noted in basal Ca ATPase activities in kidney after treatment. The capacity of target tissues in chronically treated and control rats to respond to an acute iv dose of sCT was also compared. Acute provocation tests in treated and control rats showed that the renal alkaline phosphatase response was decreased in the rats receiving long-term treatment. Moreover, the direction of response was reversed in chronically treated rats when bone alkaline phosphatase and renal Ca-dependent ATPase activity was measured after acute provocation with sCT, i.e. bone alkaline phosphatase was stimulated instead of being inhibited and renal Ca ATPase was inhibited instead of being stimulated. The application of quantitative cytochemical techniques has demonstrated intracellular changes in enzyme activities in both kidney and bone. The impaired sCT responsiveness can be detected at shorter times of treatment (1 week) and lower doses (2 IU/kg) than has previously been possible by measurement of indices of mineral metabolism in plasma or urine.

An increased turnover of phosphatidate and phosphatidyl inositol has been found in many tissues where hormones or neurotransmitters are postulated to raise Ca2+ influx, for example in smooth muscle. However, the relationship between changes in phospholipid metabolism and changes in Ca2+ permeability was unknown. Following recent reports on the interactions of Ca2+ with phosphatidic acid in membranes and artificial systems, we investigated the hypothesis that phosphatidate accumulation mediates the action of cholinergic and other stimuli on Ca2+ influx. We report here that synthesis and accumulation of phosphatidate was accelerated in smooth muscle cells stimulated by carbamylcholine with a similar time course to that of contraction. This alteration in phosphatidate metabolism does not seem to result from an increase in intracellular Ca2+ or depolarisation of the cell membrane. Furthermore, submicromolar concentrations of phosphatidate rapidly produce contractions of isolated smooth muscle cells. These results support the contention that cholinergic-induced changes in membrane Ca2+ permeability in smooth muscle could be mediated by phosphatidate accumulation.

1. Lipoproteins in the plasma of mice were characterized by agarose-gel chromatography and polyacrylamide-gel electrophoresis: genetically obese (ob/ob) mice exhibited hyperlipoproteinaemia (compared with lean mice), largely owing to an increase in the concentration of cholesterol in high-density lipoprotein. Plasma concentrations of triglyceride and phospholipid were not markedly increased in genetically obese mice. 2. The formation of glycerolipids in liver and plasma was investigated with (14)C-labelled precursors. The synthesis of hepatic triglyceride and phospholipid from glucose or palmitate was enhanced in ob/ob mice, compared with lean mice. The rate of entry of triglyceride into plasma, calculated from the time-course of incorporation of (14)C from [(14)C]palmitate into plasma triglyceride, was increased in ob/ob mice (0.5mumol of fatty acid/min, compared with 0.2 in lean mice). 3. The removal from plasma of murine lipoprotein triglyceride-[(14)C]fatty acid was increased in ob/ob mice (half-time 2.2min, compared with 7.2min in lean mice). Similar results were obtained with an injected lipid emulsion (Intralipid). 4. From these measurements, estimates of the rates of turnover of plasma triglyceride in mice (fed on a mixed diet, female, 3 months old) are about 1.0mumol of fatty acid/min in ob/ob mice, and 0.25 in lean mice. 5. The major precursor of hepatic and plasma triglyceride in lean and ob/ob mice was calculated to be plasma free fatty acid. 6. These results are discussed, in connexion with the role of the liver in triglyceride metabolism in mice, especially in relation to genetic obesity.