Mechanisms accounting for gendered differences in mental health status among young Canadians: A novel quantitative analysis.

Adolescent girls consistently report worse mental health than boys. This study used reports from a 2018 national health promotion survey (n = 11,373) to quantitatively explore why such gender-based differences exist among young Canadians. Using mediation analyses and contemporary social theory, we explored mechanisms that may explain differences in mental health between adolescents who identify as boys versus girls. The potential mediators tested were social supports within family and friends, engagement in addictive social media use, and overt risk-taking. Analyses were performed with the full sample and in specific high-risk groups, such as adolescents who report lower family affluence. Higher levels of addictive social media use and lower perceived levels of family support among girls mediated a significant proportion of the difference between boys and girls for each of the three mental health outcomes (depressive symptoms, frequent health complaints, and diagnosis of mental illness). Observed mediation effects were similar in high-risk subgroups; however, among those with low affluence, effects of family support were somewhat more pronounced. Study findings point to deeper, root causes of gender-based mental health inequalities that emerge during childhood. Interventions designed to reduce girls' addictive social media use or increase their perceived family support, to be more in line with their male peers, could help to reduce differences in mental health between boys and girls. Contemporary focus on social media use and social supports among girls, especially those with low affluence, warrant study as the basis for public health and clinical interventions.

A novel application of a data mining technique to study intersections in the social determinants of mental health among young Canadians.

OBJECTIVES: Adolescent mental health is an emergent clinical and public health priority in Canada. Gender-based differences in mental health are well established. The objective of this study was to evaluate a new data mining technique to identify social locations of young Canadians where differences in mental health between adolescent males and females were most pronounced. METHODS: We examined reports from 21,221 young Canadians aged 11-15 years (10,349 males, 10,872 females) who had responded to a 2018 national health and health behaviours survey. Using recursive partitioning for subgroup identification (SIDES), we identified social locations that were associated with the strongest differences between males and females for three reported mental health outcomes: positive psychosomatic health, symptoms of depression, and having a diagnosed mental illness. RESULTS: The SIDES algorithm identified both established and new intersections of social factors that were associated with gender-based differences in mental health experiences, most favouring males. DISCUSSION: This analysis represents a novel proof-of-concept to demonstrate the utility of a subgroup identification algorithm to reveal important differences in mental health experiences between adolescent males and females. The algorithm detected new social locations (i.e., where gender intersected with other characteristics) associated with poor mental health outcomes. These findings set the stage for further intersectional research, involving both quantitative and qualitative analyses, to explore how axes of discrimination may intersect to shape potential gender-based health inequalities that emerge during childhood.

Predicting feed intake using modelling based on feeding behaviour in finishing beef steers.

Current techniques for measuring feed intake in housed cattle are both expensive and time-consuming making them unsuitable for use on commercial farms. Estimates of individual animal intake are required for assessing production efficiency. The aim of this study was to predict individual animal intake using parameters that can be easily obtained on commercial farms including feeding behaviour, liveweight and age. In total, 80 steers were used, and each steer was allocated to one of two diets (40 per diet) which consisted of (g/kg; DM) forage to concentrate ratios of either 494:506 (MIXED) or 80:920 (CONC). Individual daily fresh weight intakes (FWI; kg/day) were recorded for each animal using 32 electronic feeders over a 56-day period, and individual DM intakes (DMI; kg/day) subsequently calculated. Individual feeding behaviour variables were calculated for each day of the measurement period from the electronic feeders and included: total number of visits to the feeder, total time spent at the feeder (TOTFEEDTIME), total time where feed was consumed (TIMEWITHFEED) and average length of time during each visit to the feeder. These feeding behaviour variables were chosen due to ease of obtaining from accelerometers. Four modelling techniques to predict individual animal intake were examined, based on (i) individual animal TOTFEEDTIME relative expressed as a proportion of the dietary group (GRP) and total GRP intake, (ii) multiple linear regression (REG) (iii) random forests (RF) and (iv) support vector regressor (SVR). Each model was used to predict CONC and MIXED diets separately, giving eight prediction models, (i) GRP_CONC, (ii) GRP_MIXED, (iii) REG_CONC, (iv) REG_MIXED, (v) RF_CONC, (vi) RF_MIXED, (vii) SVR_CONC and (viii) SVR_MIXED. Each model was tested on FWI and DMI. Model performance was assessed using repeated measures correlations (R2_RM) to capture the repeated nature of daily intakes compared with standard R2, RMSE and mean absolute error (MAE). REG, RF and SVR models predicted FWI with R2_RM = 0.1-0.36, RMSE = 1.51-2.96 kg and MAE = 1.19-2.49 kg, and DMI with R2_RM = 0.13-0.19, RMSE = 1.15-1.61 kg and MAE = 0.9-1.28 kg. The GRP models predicted FWI with R2_RM = 0.42-0.49, RMSE = 2.76-3.88 kg and MAE = 2.46-3.47 kg, and DMI with R2_RM = 0.32-0.44, RMSE = 0.32-0.44 kg, MAE = 1.55-2.22 kg. Whilst more simplistic GRP models showed higher R2_RM than regression and machine learning techniques, these models had larger errors, likely due to individual feeding patterns not being captured. Although regression and machine learning techniques produced lower errors associated with individual intakes, overall precision of prediction was too low for practical use.

A tractable covalent linker strategy for the production of immunogenic antigen-TLR7/8L bioconjugates.

Despite the ease of production and improved safety profiles of recombinant vaccines, the inherently low immunogenicity of unadjuvanted proteins remains an impediment to their widespread adoption. The covalent tethering of TLR agonists to antigenic proteins offers a unique approach to co-deliver both constituents to the same cell-enhancing vaccine efficacy while minimizing reactogenicity. However, the paucity of simple and effective linker chemistries continues to hamper progress. Here, we present a modular, PEG-based linker system compatible with even extremely lipophilic and challenging TLR7/8 agonists. To advance the field and address previous obstacles, we offer the most straightforward and antigen-preserving linker system to date. These antigen-adjuvant conjugates enhance antigen-specific immune responses in mice, demonstrating the power of our approach within the context of modern vaccinology.

Using animal-mounted sensor technology and machine learning to predict time-to-calving in beef and dairy cows.

Worldwide, there is a trend towards increased herd sizes, and the animal-to-stockman ratio is increasing within the beef and dairy sectors; thus, the time available to monitoring individual animals is reducing. The behaviour of cows is known to change in the hours prior to parturition, for example, less time ruminating and eating and increased activity level and tail-raise events. These behaviours can be monitored non-invasively using animal-mounted sensors. Thus, behavioural traits are ideal variables for the prediction of calving. This study explored the potential of two sensor technologies for their capabilities in predicting when calf expulsion should be expected. Two trials were conducted at separate locations: (i) beef cows (n = 144) and (ii) dairy cows (n = 110). Two sensors were deployed on each cow: (1) Afimilk Silent Herdsman (SHM) collars monitoring time spent ruminating (RUM), eating (EAT) and the relative activity level (ACT) of the cow, and (2) tail-mounted Axivity accelerometers to detect tail-raise events (TAIL). The exact time the calf was expelled from the cow was determined by viewing closed-circuit television camera footage. Machine learning random forest algorithms were developed to predict when calf expulsion should be expected using single-sensor variables and by integrating multiple-sensor data-streams. The performance of the models was tested using the Matthew's correlation coefficient (MCC), the area under the curve, and the sensitivity and specificity of predictions. The TAIL model was slightly better at predicting calving within a 5-h window for beef cows (MCC = 0.31) than for dairy cows (MCC = 0.29). The TAIL + RUM + EAT models were equally as good at predicting calving within a 5-h window for beef and dairy cows (MCC = 0.32 for both models). Combining data-streams from SHM and tail sensors did not substantially improve model performance over tail sensors alone; therefore, hour-by-hour algorithms for the prediction of time of calf expulsion were developed using tail sensor data. Optimal classification occurred at 2 h prior to calving for both beef (MCC = 0.29) and dairy cows (MCC = 0.25). This study showed that tail sensors alone are adequate for the prediction of parturition and that the optimal time for prediction is 2 h before expulsion of the calf.

Understanding clusters of risk factors across different environmental and social contexts for the prediction of injuries among Canadian youth.

BACKGROUND: Among Canadian youth, injury is the most common reason for presentation to the emergency department. Youth who commonly engage in multiple risk-taking behaviours are at greater risk for injury, but is it unknown if this phenomenon is more pronounced in different contexts. We aimed to study relationships between risk-taking behaviours and injury, and variations in such relationships between different environmental and social contexts, among youth in Canada. METHODS: Risk-taking behaviour and injury outcome data were collected from grade 9 to 10 students using the 2009-2010 (Cycle 6) of the Health Behaviour in School-Aged Children Survey (n=10,429). Principal components analysis was used to identify clusters of risk-taking behaviours. Within each identified cluster, the degree of risk-taking was categorized into quartiles from lowest to highest engagement in the behaviours. Risk ratios with 95% confidence intervals were calculated to determine the association between the risk of any injury and the degree of risk-taking behaviour specific to the cluster. Clusters were then examined across home, school, neighbourhood and sport contexts. RESULTS: Four clusters of risk-taking behaviour were identified which were labelled as "gateway substance use", "hard drugs and weapons", "overt risk-taking", and "physical activity". Each cluster was related to injury occurrence in a graded fashion. Clusters of risk behaviour were most strongly associated with injuries sustained in neighbourhood settings, and expectedly, increasing physical activity behaviours were associated with increased risk of sport injuries and injuries occurring at school. CONCLUSIONS: This study furthers understanding of clustered risk-taking phenomena that put youth at increasing levels of injury risk. Higher risks for injury and associated gradients were observed in less structured contexts such as neighbourhoods. In contrast, clustered physical activity behaviours were most related to school injury or sport injury and were more likely to be sustained in a supervised context. Understanding the clustered and cumulative nature of risk-behaviours, and how these vary by environmental and social context, helps to explain potential mechanisms of injury as well as modifiable factors that may be important avenues for intervention.

A Simple Evaluation Tool (ET-CET) Indicates Increase of Diagnostic Skills From Small Bowel Capsule Endoscopy Training Courses: A Prospective Observational European Multicenter Study.

Small bowel capsule endoscopy (SBCE) has become a first line diagnostic tool. Several training courses with a similar format have been established in Europe; however, data on learning curve and training in SBCE remain sparse.Between 2008 and 2011, different basic SBCE training courses were organized internationally in UK (n = 2), Italy (n = 2), Germany (n = 2), Finland (n = 1), and nationally in Germany (n = 10), applying similar 8-hour curricula with 50% lectures and 50% hands-on training. The Given PillCam System was used in 12 courses, the Olympus EndoCapsule system in 5, respectively. A simple evaluation tool for capsule endoscopy training (ET-CET) was developed using 10 short SBCE videos including relevant lesions and normal or irrelevant findings. For each video, delegates were required to record a diagnosis (achievable total score from 0 to 10) and the clinical relevance (achievable total score 0 to 10). ET-CET was performed at baseline before the course and repeated, with videos in altered order, after the course.Two hundred ninety-four delegates (79.3% physicians, 16.3% nurses, 4.4% others) were included for baseline analysis, 268 completed the final evaluation. Forty percent had no previous experience in SBCE, 33% had performed 10 or less procedures. Median scores for correct diagnosis improved from 4.0 (IQR 3) to 7.0 (IQR 3) during the courses (P < 0.001, Wilcoxon), and for correct classification of relevance of the lesions from 5.0 (IQR 3) to 7.0 (IQR 3) (P < 0.001), respectively. Improvement was not dependent on experience, profession, SBCE system, or course setting. Previous experience in SBCE was associated with higher baseline scores for correct diagnosis (P < 0.001; Kruskal-Wallis). Additionally, independent nonparametric partial correlation with experience in gastroscopy (rho 0.33) and colonoscopy (rho 0.27) was observed (P < 0.001).A simple ET-CET demonstrated significant improvement of diagnostic skills on completion of formal basic SBCE courses with hands-on training, regardless of preexisting experience, profession, and course setting. Baseline scores for correct diagnoses show a plateau after interpretation of 25 SBCE before courses, supporting this number as a compromise for credentialing. Experience in flexible endoscopy may be useful before attending an SBCE course.

Multimodal optical, X-ray CT, and SPECT imaging of a mouse model of breast cancer lung metastasis.

Tumor heterogeneity is recognized as a major issue within clinical oncology, and the concept of personalized molecular medicine is emerging as a means to mitigate this problem. Given the vast number of cancer types and subtypes, robust pre-clinical models of cancer must be studied to interrogate the molecular mechanisms involved in each scenario. In particular, mouse models of tumor metastasis are of critical importance for pre-clinical cancer research at the cancer cell molecular level. In many of these experimental systems, tumor cells are injected intravenously, and the distribution and proliferation of these cells are subsequently analyzed via ex vivo methods. These techniques require large numbers of animals coupled with time-consuming histological preparation and analysis. Herein, we demonstrate the use of two facile and noninvasive imaging techniques to enhance the study of a pre-clinical model of breast cancer metastasis in the lung. Breast cancer cells were labeled with a near-infrared fluorophore that enables their visualization. Upon injection into a living mouse, the distribution of the cells in the body was detected and measured using whole animal fluorescence imaging. X-ray computed tomography (CT) was subsequently used to provide a quantitative measure of longitudinal tumor cell accumulation in the lungs over six weeks. A nuclear probe for lung perfusion, 99mTc-MAA, was also imaged and tested during the time course using single photon emission computed tomography (SPECT). Our results demonstrate that optical fluorescence methods are useful to visualize cancer cell distribution patterns that occur immediately after injection. Longitudinal imaging with X-ray CT provides a convenient and quantitative avenue to measure tumor growth within the lung space over several weeks. Results with nuclear imaging did not show a correlation between lung perfusion (SPECT) and segmented lung volume (CT). Nevertheless, the combination of animal models and noninvasive optical and CT imaging methods provides better research tools to study cancer cell differences at the molecular level. Ultimately, the knowledge gleaned from these improved studies will aid researchers in uncovering the mechanisms mediating breast cancer metastasis, and eventually improve the treatments of patients in the clinic.

Introducing personalised care planning into Newham: outcomes of a pilot project.

AIM: To explore the feasibility and acceptability of implementing a personalised care planning approach for diabetes care in general practice. METHODS: A four-stage care planning process was introduced for diabetes annual review, involving patients (1) being made aware of the new process, (2) attending an appointment to gather clinical data, (3) receiving and reviewing their results and (4) attending a care planning consultation. The latter is a collaborative discussion with the health professional about their response to their results, their goals and desired action plan. Health professionals received specialist training in personalised care planning, including practice observations and feedback. RESULTS: Sixty-six per cent of patients eligible to participate in the project attended both appointments and received an annual review. Of these, 89% also agreed a personalised care plan. Staff reported greater engagement among patients who had read and understood their results. Fourteen per cent of patients reported that they had not agreed a care plan but would have liked one. Patients reported increased confidence in managing their condition with 75% feeling that their ideas and goals were discussed completely. CONCLUSIONS: Introducing personalised care planning to general practice diabetes care is possible and well received. Our model for implementation of personalised care planning, which includes specialist training for practice teams and ongoing support from local colleagues and health organizations, can help to meet national recommendations for the provision of personalised care plans for people with long-term conditions. When implementing personalised care planning, efficient administration is vital and behaviour change is necessary for both staff and patients.

Note: fast, small, and low vibration mechanical laser shutters.

We present three novel mechanical laser shutter designs based, respectively, on a stepper motor, a relay, and a piezoelectric actuator. Each shutter type is ideally suited to a specific shuttering application. The stepper motor is well suited for applications requiring low vibrations, the relay is compact and capable of rapid bursts, and the piezoelectric is 2 orders of magnitude faster than other available mechanical shutters.

Surfactant therapy for bronchiolitis in critically ill infants.

BACKGROUND: Viral bronchiolitis is a common cause of respiratory failure in infants and children, and accounts for a significant portion of intensive care unit (ICU) admissions during seasonal epidemics. Currently there is no evidence to support the use of anything but supportive care for this disease. Surfactant is a potentially promising therapy; alterations in its composition have been described in bronchiolitis, and it may play a role in the host immunity for this disease. OBJECTIVES: The objective of this review was to assess the efficacy of exogenous surfactant for the treatment of bronchiolitis in mechanically ventilated infants and children. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2006); MEDLINE (1966 to Week 1, February 2006); and EMBASE (1990 to September 2005). We reviewed reference lists of relevant articles and contacted experts in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing surfactant with placebo or surfactant with no surfactant in mechanically ventilated infants and children with viral bronchiolitis. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed trial quality. Unpublished data were requested from trial authors when necessary. MAIN RESULTS: Three trials containing a total of 79 patients met the inclusion criteria. No mortality or adverse effects associated with surfactant administration were reported in any of these trials. In the three trials, use of surfactant was associated with a decrease in duration of mechanical ventilation by 2.6 days (95% confidence interval (CI) -5.34 to 0.18 days; P value 0.07) and a decrease in ICU length of stay by 3.3 days (95% CI -6.38 to -0.23 days; P value 0.04). In two studies with 59 patients, in which duration of mechanical ventilation in the control groups was more comparable, surfactant was associated with a decrease in ventilator days by 1.21 days (95% CI 0.75 to 1.67 days) and a decrease in ICU stay by 1.81 days (95% CI 1.19 days to 2.42 days). Individually the studies reported some short term benefit of surfactant on pulmonary mechanics and gas exchange. AUTHORS' CONCLUSIONS: Available data on surfactant were not sufficient to provide reliable estimates of its effects in mechanically ventilated infants and children with bronchiolitis. Future studies should be adequately powered and will need to address unresolved questions regarding which surfactant preparation may be best suited for the treatment of bronchiolitis, the appropriate dose and administration interval, and how the choice of ventilator strategy may modify its effects.

In vivo skin absorption and distribution of the nerve agent VX (O-ethyl-S-[2(diisopropylamino)ethyl] methylphosphonothioate) in the domestic white pig.

The purpose of this study was to characterize the skin absorption and distribution of VX (O-ethyl-S-[2 (diisopropylamino)ethyl] methylphosphonothioate) in the domestic pig in order to evaluate the animal as a potential model for assessing pretreatments against toxic anti-cholinesterase compounds. A liquid droplet (equivalent to a 2 x LD50 dose) of radiolabelled VX was applied to the inner ear-skin of each anaesthetized animal. Blood and tissue samples (liver, lung, kidney, heart and skin exposure sites) were obtained post-mortem. The amount of radioactivity in each sample was measured by liquid scintillation counting, from which the skin absorption rate and dose distribution of VX were calculated. A substantial proportion (22 +/- 3%) of the applied dose remained within the skin at the site of application. It is conceivable that strategies to minimize or remove this reservoir may be of benefit in the early treatment of VX-exposed casualties. Image analysis of autoradiographs of exposed skin sites indicated that each milligram of radioactive VX covered an area of 1.2 +/- 0.5 cm2. The average skin absorption rate of 14C-VX was 661 +/- 126 microg/cm2 per hour. Comparison of these data with previous studies suggests that human skin is less permeable to VX than pig skin, but VX spreads over a greater surface area when applied to human skin. Thus, paradoxically, while pig-ear skin is more permeable than human skin, the difference in skin surface spreading may lead to the absorption of an equivalent systemic dose.

The effect of changing from one to two views at incident (subsequent) screens in the NHS breast screening programme in England: impact on cancer detection and recall rates.

AIM: To assess the effect on cancer detection and recall rates of changing from one to two views for incident (subsequent) screens. METHODS: Controlled, comparative, observational study of programmes in NHS breast screening programme in England. SUBJECTS: women aged 50-64 years were screened by the NHSBSP between 1 April 2001 and 31 March 2003. RESULTS: The effect of changing to two-view mammography was a 20% increase in overall incident screen cancer detection rate, with the biggest effect seen for small (<15 mm) invasive cancers. This increased detection rate was achieved with an 11% drop-in recall rate. CONCLUSION: The introduction of two-view mammography for incident screens has resulted in considerable improvements in overall NHS breast screening performance.

Do silicone breast implants cause rheumatologic disorders? A systematic review for a court-appointed national science panel.

OBJECTIVE: To assist in evaluating expert testimony and scientific evidence presented in law suits brought against silicone breast implant manufacturers, a US District Court Order established a National Science Panel to assess whether existing studies provide scientific evidence of an association between silicone breast implants and systemic classic/accepted connective disease, atypical connective disease, and certain signs and symptoms identified by plaintiffs in the law suits. Local disorders potentially associated with these implants were not addressed in this review. Therefore, we performed a systematic review of published studies on the association between silicone breast implants and systemic connective tissue disorders. METHODS: Data from relevant studies (human cohort, case-control, or cross-sectional studies with > or = 10 participants and appropriate controls) were identified through literature searches of Medline, Current Contents, HealthStar, Biological Abstracts, EMBase, Toxline, and Dissertation Abstracts. Two independent reviewers, using standard collection forms, extracted data from the included studies. Adjusted relative risks (RRs) in cohort studies and odds ratios (ORs) in case-control and cross-sectional studies were reported if provided; otherwise, unadjusted RRs and ORs were calculated. RESULTS: Twenty-four studies meeting inclusion criteria were identified. No association was evident between breast implants and any established or atypical connective tissue disorder. There was discordance among studies in reports of arthralgias, lymphadenopathy, myalgias, sicca symptoms, skin changes, and stiffness. CONCLUSION: The panel found no evidence to support expert testimony suggesting an association between silicone breast implants and connective diseases. Discordance for symptoms may reflect differences in symptoms included in various categories, the small number of cases, and the effect of having single subjects with > 1 symptom represented in analyses of each symptom reported. The process presented here is an early example of the use of independent scientific panels to help courts clarify scientific evidence in legal proceedings.

A radiation hybrid map of mouse genes.

A comprehensive gene-based map of a genome is a powerful tool for genetic studies and is especially useful for the positional cloning and positional candidate approaches. The availability of gene maps for multiple organisms provides the foundation for detailed conserved-orthology maps showing the correspondence between conserved genomic segments. These maps make it possible to use cross-species information in gene hunts and shed light on the evolutionary forces that shape the genome. Here we report a radiation hybrid map of mouse genes, a combined project of the Whitehead Institute/Massachusetts Institute of Technology Center for Genome Research, the Medical Research Council UK Mouse Genome Centre, and the National Center for Biotechnology Information. The map contains 11,109 genes, screened against the T31 RH panel and positioned relative to a reference map containing 2,280 mouse genetic markers. It includes 3,658 genes homologous to the human genome sequence and provides a framework for overlaying the human genome sequence to the mouse and for sequencing the mouse genome.

A comparison of stereoscopic and monoscopic evaluation of optic disc topography using a digital optic disc stereo camera.

AIMS: To compare stereophotographic and monophotographic optic disc assessments made using a digital optic disc stereo camera. METHODS: Stereo digital optic disc photographs of 150 selected patients who had presented to a glaucoma clinic were assessed by two masked observers on separate occasions using (1) the stereophotographs and a stereoviewer, (2) a single image from the same stereopair. Results were analysed for both right and left eyes separately. 95% tolerance limits for change (TC) and intraclass correlation coefficients (ICC) were calculated and a multivariate analysis using a general linear model for repeated measures was performed. RESULTS: A total of 201 optic disc images of 150 patients (84 females, 108 left eyes) were analysed. Mean age of patients was 64 years. The results for right eyes are as follows (similar results were obtained for left eyes). Intraobserver (stereoscopic compared to monoscopic) measurements of: horizontal cup:disc ratios (CDR), ICC = 0.5995 and 0.7269, TC = 34% and 27%; vertical CDR, ICC = 0.8298 and 0.817, TC = 25% and 27%; area CDR, ICC = 0.7757 and 0.8259, TC = 28% and 25%; circumference CDR, ICC = 0.7618 and 0.8103, TC = 28% and 25%. Interobserver measurements of: horizontal CDR, ICC stereoscopic (SS) = 0.7287; monoscopic (MS) = 0.5030; TC SS = 30%; MS = 32%; vertical CDR, ICC SS = 0.8439; MS = 0.7106; TC SS = 25%; MS = 31%; area CDR, ICC SS = 0.8392; MS = 0.6276; TC SS = 26%; MS = 32%; circumference CDR, ICC SS = 0.8433; MS = 0.6438, TC SS = 26%; MS = 31%. Systematic bias between observers and between methods was within acceptable limits. CONCLUSIONS: This study using a digital stereo camera indicates that there may be little benefit of stereoscopic imaging over monoscopic imaging despite demonstrating small but inconsistent differences between both observers and methods.

Inhibition of neurogenic inflammation by the Amazonian herbal medicine sangre de grado.

UNLABELLED: This study was designed to determine if the Amazonian medicinal sangre de grado, confers benefit by suppressing the activation of sensory afferent nerves. METHODS: (i) vasorelaxation of rat mesenteric arteries in response to calcitonin gene-related peptide; (ii) rat paw edema in response to protease- activating peptide receptor 2-activating peptide; (iii) rat paw hyperalgesia in response to low-dose protease-activating peptide receptor 2-activating peptide or prostaglandin E2; (iv) gastric hyperemia in response luminal capsaicin; (v) a clinical trial of a sangre de grado balm in pest control workers. The parent botanical was fractionated for evaluation of potential active components. In preconstricted rat mesenteric arteries, highly diluted sangre de grado (1:10,000) caused a shift to the right of the calcitonin gene-related peptide dose-response curve (p < 0.01). Paw edema in response to protease-activating peptide receptor 2-activating peptide (500 microg) was reduced by as single topical administration sangre de grado balm (1% concentration, p < 0.01) for at least 6 h. Hyperalgesia induced by either low-dose protease-activating peptide receptor 2-activating peptide (50 microg) or prostaglandin E2 was prevented by sangre de grado balm. A fraction possessing analgesic and capsaicin antagonistic properties was isolated and high-performance liquid chromatography and gas chromatography-mass spectrometry analysis indicated that it was a proanthocyandin oligomer. In pest control workers, sangre de grado balm (Zangrado) was preferred over placebo, for the relief of itching, pain, discomfort, edema, and redness in response to wasps, fire ants, mosquitoes, bees, cuts, abrasions, and plant reactions. Subjects reported relief within minutes. We conclude that sangre de grado is a potent inhibitor of sensory afferent nerve mechanisms and supports its ethnomedical use for disorders characterized by neurogenic inflammation.

Effect of age on electrical field stimulation (EFS)-induced endothelium-dependent vasodilation in male and female rats.

OBJECTIVE: The purpose of this study was to determine whether the effect of age on electrical field stimulation (EFS)-induced endothelium-dependent vasodilation was different in males and females. METHODS: Young (3 month) and old (25 month) Fisher 344 rats were studied: young females (YF, n=34), young males (YM, n=28), old females (OF, n=19), and old males (OM, n=24). Isolated mesenteric resistance arteries (endothelium-intact and denuded) were pressurized, and outer diameter was monitored. EFS-response curves (0.1-8 Hz) were performed in preconstricted arteries in the presence of guanethidine. EFS responses were expressed as percent relaxation from preconstricted diameter. Area under the curve (AUC) was calculated and comparisons were made using ANOVA and t-tests. RESULTS: Males became less responsive to EFS-induced vasodilation with age, while responses among females were unaffected (AUC: YM=344+/-23, OM=253+/-25, P=0.008; YF=397+/-21, OF=365+/-25, P=0.33). Endothelial denudation produced a significant decrease in EFS-induced dilation among all rat groups. The effect of denudation was greater in young animals compared to old. Incubation with the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine (LNA) significantly decreased EFS responsiveness among all of the rat groups. CONCLUSIONS: EFS-induced vasodilation declines with age among males. In YF and YM endothelium-dependent EFS-induced vasodilation is mediated by the release of endothelium-derived NO. With age, endothelial function declines, which is likely due to a decrease in the production of endothelium-derived NO. A decline in endothelial-derived NO is likely responsible for the decrease in EFS-induced vasodilation with age among males.

Gender differences in the effect of age on electrical field stimulation (EFS)-induced adrenergic vasoconstriction in rat mesenteric resistance arteries.

The objective of this study was to examine the effects of gender and age on electrical field stimulation (EFS)-induced vasoconstriction. Fisher 344 rats were studied: young females (YF, n = 38), young males (YM, n = 29), old females (OF, n = 33), and old males (OM, n = 30). Isolated mesenteric resistance arteries (endothelium-intact or denuded) were pressurized, and outer diameter was monitored. Dose-response curves were performed to KCl and phenylephrine (PE). EFS (0.1-16 Hz) responses were expressed as percentage of constriction from baseline. Area under the curve (AUC) was calculated and comparisons were made using analysis of variance and t tests. Females became less responsive to EFS-induced constriction with age, whereas constrictor responses among males were unaffected (AUC: YF = 454 +/- 15, OF = 284 +/- 22, p < 0.001; YM = 391 +/- 35, OM = 357 +/- 31, p = 0.22). Endothelial denudation produced a significant increase in EFS-induced constriction in OF and OM. Endothelium removal in OF increased the EFS constrictor response to the level seen in arteries from YF. BQ 123 (ET(A) receptor antagonist) significantly decreased EFS-induced constriction in YM and OM. In YM, SQ 29,548 [thromboxane A(2) (TXA(2))/PGH(2) receptor antagonist] and indomethacin depressed constrictor responses. There were no differences among groups in the sensitivity to KCl, but YF were the most sensitive to PE. In conclusion, EFS-induced vasoconstriction declined with age among females but not males. The decrease in EFS constrictor responses in OF may be due to a selective decrease in vascular smooth muscle sensitivity to adrenergic agonists and an increase in the production of an endothelium-derived vasodilator. Among males there is also an endothelin-1 and TXA(2)/PGH(2) component to EFS-induced constriction that is absent among females.