Induction of chronic migraine phenotypes in a rat model after environmental irritant exposure

Air pollution is linked to increased emergency department visits for headache and migraine patients frequently cite chemicals or odors as headache triggers, but the association between air pollutants and headache is not well understood. We previously reported that chronic environmental irritant exposure sensitizes the trigeminovascular system response to nasal administration of environmental irritants. Here, we examine whether chronic environmental irritant exposure induces migraine behavioral phenotypes. Male rats were exposed to acrolein, a transient receptor potential channel ankyrin-1 (TRPA1) agonist, or room air by inhalation for 4 days before meningeal blood flow measurements, periorbital cutaneous sensory testing, or other behavioral testing. Touch-induced c-Fos expression in trigeminal nucleus caudalis was compared in animals exposed to room air or acrolein. Spontaneous behavior and olfactory discrimination was examined in open-field testing. Acrolein inhalation exposure produced long-lasting potentiation of blood flow responses to a subsequent TRPA1 agonist and sensitized cutaneous responses to mechanical stimulation. C-Fos expression in response to touch was increased in trigeminal nucleus caudalis in animals exposed to acrolein compared with room air. Spontaneous activity in an open-field and scent preference behavior was different in acrolein-exposed compared with room air-exposed animals. Sumatriptan, an acute migraine treatment blocked acute blood flow changes in response to TRPA1 or transient receptor potential vanilloid receptor-1 agonists. Pretreatment with valproic acid, a prophylactic migraine treatment, attenuated the enhanced blood flow responses observed after acrolein inhalation exposures. Environmental irritant exposure yields an animal model of chronic migraine in which to study mechanisms for enhanced headache susceptibility after chemical exposure

Management of atrial fibrillation in diabetes

Diabetes is an important risk factor for cardiovascular morbidity and mortality, and atrial fibrillation is linked to cardiovascular complications. The prevalence of both is increasing and they commonly co‐exist with a longer duration of diabetes and poorer control putting individuals at higher risk of atrial fibrillation. The complications of atrial fibrillation include heart failure and thromboembolism. There is an association between diabetes and atrial fibrillation and there are many theories as to the specific pathophysiology, including sharing similar precursors, but it is not clearly understood. What is understood is that the risk of developing the main consequences of atrial fibrillation can be reduced by treatment. Broadly speaking, this involves controlling the heart rhythm and/or heart rate to improve cardiac function in addition to anticoagulation. The development of risk stratification strategies and direct oral anticoagulants has led to safer anticoagulation with more individuals thought to benefit balanced against any potential risk of bleeding. The evidence base for treatment of atrial fibrillation includes many individuals with diabetes and, in this group, prevention of complications is equally as relevant. In those with diabetes and atrial fibrillation the evidence overwhelmingly supports a treatment strategy similar to that for individuals with atrial fibrillation but without diabetes. This should be done in addition to identifying and treating other cardiovascular risk factors

The Trombones of the Saint Louis Symphony Orchestra

Kemp Recital Hall Thursday Evening January 17, 2008 8:00p.m

Exceptional longevity and potential determinants of successful ageing in a cohort of 39 Labrador retrievers: results of a prospective longitudinal study.

BACKGROUND: The aim of this study was to describe the longevity and causes of mortality in 39 (12 males, 27 females) pedigree adult neutered Labrador retrievers with a median age of 6.5 years at the start of the study and kept under similar housing and management conditions. Body condition score was maintained between two and four on a 5-point scale by varying food allowances quarterly. The impact of change in body weight (BW) and body composition on longevity was analysed using linear mixed models with random slopes and intercepts. RESULTS: On 31 July 2014, 10 years after study start, dogs were classified into three lifespan groups: 13 (33 %) Expected (≥9 to ≤12.9 years), 15 (39 %) Long (≥13 to ≤15.5 years) and 11 (28 %) Exceptional (≥15.6 years) with five still alive. Gender and age at neutering were not associated with longevity (P ≥ 0.06). BW increased similarly for all lifespan groups up to age 9, thereafter, from 9 to 13 years, Exceptional dogs gained and Long-lifespan dogs lost weight (P = 0.007). Dual-energy x-ray absorptiometer scans revealed that absolute fat mass increase was slower to age 13 for Long compared with Expected lifespan dogs (P = 0.003) whilst all groups lost a similar amount of absolute lean mass (P > 0.05). Percent fat increase and percent lean loss were slower, whilst the change in fat:lean was smaller, in both the Exceptional and Long lifespan compared with Expected dogs to age 13 (P ≤ 0.02). Total bone mineral density was significantly lower for Expected compared to Exceptional and Long lifespan dogs (P < 0.04). CONCLUSIONS: This study shows that life-long maintenance of lean body mass and attenuated accumulation of body fat were key factors in achieving a longer lifespan. The results suggest that a combination of a high quality plane of nutrition with appropriate husbandry and healthcare are important in obtaining a greater than expected proportion of Labrador retrievers living well beyond that of the expected breed lifespan: 89.7 % (95 % CI 74.8-96.7 %) dogs were alive at 12 years of age and 28.2 % (95 % CI 15.6-45.1 %) reaching an exceptional lifespan of ≥15.6 years.The authors wish to thank all the former P&G Research & Development team involved for their assistance in this study since its inception over 10 years ago. The authors also wish to acknowledge the role of P&G for their financial support of this study and Spectrum Brands for supporting the analysis and preparation of this manuscript.This is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/s13028-016-0206-

Sensitization of the Trigeminovascular System following Environmental Irritant Exposure

Background Air pollution is linked to increased emergency room visits for headache, and migraine patients frequently cite chemicals or odors as headache triggers, but the association between air pollutants and headache is not well understood. We previously reported that nasal administration of environmental irritants acutely increases meningeal blood flow via a TRPA1-dependent mechanism involving the trigeminovascular system. Here, we examine whether chronic environmental irritant exposure sensitizes the trigeminovascular system. Methods Male rats were exposed to acrolein, a TRPA1 agonist, or room air by inhalation for four days prior to meningeal blood flow measurements. Some animals were injected daily with a TRPA1 antagonist, AP-18, or vehicle prior to inhalation exposure. Trigeminal ganglia were isolated following blood flow measurements for immunocytochemistry and/or qPCR determination of TRPV1, TRPA1 and CGRP levels. Results Acrolein inhalation exposure potentiated blood flow responses both to TRPA1 and TRPV1 agonists compared to room air. Acrolein exposure did not alter TRPV1 or TRPA1 mRNA levels or TRPV1 or CGRP immunoreactive cell counts in the trigeminal ganglion. Acrolein sensitization of trigeminovascular responses to a TRPA1 agonist was attenuated by pre-treatment with AP-18. Interpretation These results suggest trigeminovascular sensitization as a mechanism for enhanced headache susceptibility after chemical exposure

Role of intraganglionic transmission in the trigeminovascular pathway

Migraine is triggered by poor air quality and odors through unknown mechanisms. Activation of the trigeminovascular pathway by environmental irritants may occur via activation of transient receptor potential ankyrin 1 (TRPA1) receptors on nasal trigeminal neurons, but how that results in peripheral and central sensitization is unclear. The anatomy of the trigeminal ganglion suggests that noxious nasal stimuli are not being transduced to the meninges by axon reflex but likely through intraganglionic transmission. Consistent with this concept, we injected calcitonin gene-related peptide, adenosine triphosphate, or glutamate receptor antagonists or a gap junction channel blocker directly and exclusively into the trigeminal ganglion and blocked meningeal blood flow changes in response to acute nasal TRP agonists. Previously, we observed chronic sensitization of the trigeminovascular pathway after acrolein exposure, a known TRPA1 receptor agonist. To explore the mechanism of this sensitization, we utilized laser dissection microscopy to separately harvest nasal and meningeal trigeminal neuron populations in the absence or presence of acrolein exposure. mRNA levels of neurotransmitters important in migraine were then determined by reverse transcription polymerase chain reaction. TRPA1 message levels were significantly increased in meningeal cell populations following acrolein exposure compared to room air exposure. This was specific to TRPA1 message in meningeal cell populations as changes were not observed in either nasal trigeminal cell populations or dorsal root ganglion populations. Taken together, these data suggest an important role for intraganglionic transmission in acute activation of the trigeminovascular pathway. It also supports a role for upregulation of TRPA1 receptors in peripheral sensitization and a possible mechanism for chronification of migraine after environmental irritant exposure

Predicting Scenarios for Successful Autodissemination of Pyriproxyfen by Malaria Vectors from Their Resting Sites to Aquatic Habitats; Description and Simulation Analysis of a Field-Parameterizable Model

Background Large-cage experiments indicate pyriproxifen (PPF) can be transferred from resting sites to aquatic habitats by Anopheles arabiensis - malaria vector mosquitoes to inhibit emergence of their own offspring. PPF coverage is amplified twice: (1) partial coverage of resting sites with PPF contamination results in far higher contamination coverage of adult mosquitoes because they are mobile and use numerous resting sites per gonotrophic cycle, and (2) even greater contamination coverage of aquatic habitats results from accumulation of PPF from multiple oviposition events. Methods and Findings Deterministic mathematical models are described that use only field-measurable input parameters and capture the biological processes that mediate PPF autodissemination. Recent successes in large cages can be rationalized, and the plausibility of success under full field conditions can be evaluated a priori. The model also defines measurable properties of PPF delivery prototypes that may be optimized under controlled experimental conditions to maximize chances of success in full field trials. The most obvious flaw in this model is the endogenous relationship that inevitably occurs between the larval habitat coverage and the measured rate of oviposition into those habitats if the target mosquito species is used to mediate PPF transfer. However, this inconsistency also illustrates the potential advantages of using a different, non-target mosquito species for contamination at selected resting sites that shares the same aquatic habitats as the primary target. For autodissemination interventions to eliminate malaria transmission or vector populations during the dry season window of opportunity will require comprehensive contamination of the most challenging subset of aquatic habitats that persist or retain PPF activity (Ux) for only one week , where Ux = 7 days). To achieve >99% contamination coverage of these habitats will necessitate values for the product of the proportional coverage of the ovipositing mosquito population with PPF contamination (CM) by the ovitrap-detectable rates of oviposition by wild mosquitoes into this subset of habitats , divided by the titre of contaminated mosquitoes required to render them unproductive , that approximately approach unity . Conclusions The simple multiplicative relationship between CM and , and the simple exponential decay effect they have upon uncontaminated aquatic habitats, allows application of this model by theoreticians and field biologists alike