Role of the aryl hydrocarbon receptor in Sugen 5416-induced experimental pulmonary hypertension

Rationale: Rats dosed with the vascular endothelial growth factor (VEGF) inhibitor Sugen 5416 (Su), placed in hypoxia then restored to normoxia has become a widely used model of pulmonary arterial hypertension (PAH). The mechanism by which Su exaccerbates pulmonary hypertension is, however, unclear. Objectives: We investigated Su-activation of the aryl hydrocarbon receptor (AhR) in patient human pulmonary arterial smooth muscle cells (hPASMCs) and patient blood outgrowth endothelial cells (BOECs). We also examined the effect of AhR on aromatase and estrogen levels in the lung. Methods, Measurements and Main Results: Protein and mRNA analysis demonstrated that CYP1A1 was very highly induced in the lungs of Su/hypoxic (Su/Hx) rats. The AhR antagonist CH223191 (8mg/kg/day) reversed the development of PAH in this model in vivo and normalized lung CYP1A1 expression. Increased lung aromatase and estrogen levels in Su/Hx rats were also normalized by CH223191 as was AhR nuclear translocator (ARNT [HIF-1β]) which is shared by HIF-1α and AhR. Su reduced HIF1α expression in hPASMCs. Su induced proliferation in BOECs and increased apoptosis in human pulmonary microvascular endothelial cells (hPMECs) and also induced translocation of AhR to the nucleus in hPASMCs. Under normoxic conditions, hPASMCs do not proliferate to Su. However when grown in hypoxia (1%) Su induced hPASMC proliferation. Conclusion: In combination with hypoxia, Su is proliferative in patient hPASMCs and patient BOECs and Su/Hx-induced PAH in rats may be facilitated by AhR-induced CYP1A1, ARNT and aromatase. Inhibition of the AhR receptor may be a novel approach to the treatment of pulmonary hypertension

Improved Knowledge and Adoption of Recommended Food Safety Practices by Food Recovery Agency Personnel and Volunteers Participating in the Serving Food Safely Program

The tri-state study reported here tested the effectiveness of a curriculum developed and presented in workshops by Extension and research faculty to increase knowledge and promote safe food handling practices of staff and volunteers of food recovery agencies providing rescued and surplus food to vulnerable populations. Results indicated that knowledge and adoption of recommended food safety practices increased for both staff and volunteers following participation in the workshops. The improvement in food safety knowledge and adoption of recommended food safety practices support the continued use of the food safety curriculum in the three states and possibly other areas in the United States

Upper Body Muscular Activation during Variations of Push-Ups in Healthy Men

International Journal of Exercise Science 6(4) : 278-288, 2013. The purpose of this study was to assess neural activity for upper body musculature in college-age men during repetitions of a conventional pushup or a Perfect PushupTM. Eighteen healthy men (21.6±1 yr, 182.5±7 cm, 87.4±15 kg) completed five repetitions of a conventional pushup and Perfect PushupTM while using a wide hand base of support for the upper body. Body position, hand placement, and cadence of the pushup were standardized. Root mean square electromyography (RMS-EMG, mV/Sec) was collected for the triceps brachii (TB), pectoralis major (PM), serratus anterior (SA), and posterior deltoid (PD) during all repetitions. RMS-EMG values were normalized to a maximal voluntary isometric contraction in the pushup position (%MVICPU). For each muscle, %MVICPU for repetitions 1, 3, and 5 were analyzed for differences due to type of push-up. No differences in %MVICPU due to type ofpush-up for the TB (p=0.079) or the SA (p=0.45) were detected. The Perfect PushupTM increased %MVICPU compared to the conventional pushup (44%, p\u3c0.05). Additionally, the Perfect PushupTM increased %MVICPU by the third repetition (p\u3c0.05) while the conventional pushup did not until the 5th repetition. The conventional pushup activated more PD (76%, p\u3c0.05). The type of push-up that requires the greatest neural activity for a given number of repetitions should result in improved adaptations. The Perfect PushupTM was superior for activating the pectoralis major while individuals would elicit more neural activation in the posterior deltoid by conventional push-ups. Trainers and rehabilitation specialists should consider these data when attempting to train or isolate upper body skeletal muscles using a push-up movement

The serotonin transporter promotes a pathological estrogen metabolic pathway in pulmonary hypertension via cytochrome P450 1B1 pulmonary circulation

Pulmonary arterial hypertension (PAH) is a devastating vasculopathy that predominates in women and has been associated with dysregulated estrogen and serotonin signaling. Overexpression of the serotonin transporter (SERT+) in mice results in an estrogen-dependent development of pulmonary hypertension (PH). Estrogen metabolism by cytochrome P450 1B1 (CYP1B1) contributes to the pathogenesis of PAH, and serotonin can increase CYP1B1 expression in human pulmonary arterial smooth muscle cells (hPASMCs). We hypothesized that an increase in intracellular serotonin via increased SERT expression may dysregulate estrogen metabolism via CYP1B1 to facilitate PAH. Consistent with this hypothesis, we found elevated lung CYP1B1 protein expression in female SERT+ mice accompanied by PH, which was attenuated by the CYP1B1 inhibitor 2,3',4,5'-tetramethoxystilbene (TMS). Lungs from female SERT+ mice demonstrated an increase in oxidative stress that was marked by the expression of 8-hydroxyguanosine; however, this was unaffected by CYP1B1 inhibition. SERT expression was increased in monocrotaline-induced PH in female rats; however, TMS did not reverse PH in monocrotaline-treated rats but prolonged survival. Stimulation of hPASMCs with the CYP1B1 metabolite 16α-hydroxyestrone increased cellular proliferation, which was attenuated by an inhibitor (MPP) of estrogen receptor alpha (ERα) and a specific ERα antibody. Thus, increased intracellular serotonin caused by increased SERT expression may contribute to PAH pathobiology by dysregulation of estrogen metabolic pathways via increased CYP1B1 activity. This promotes PASMC proliferation by the formation of pathogenic metabolites of estrogen that mediate their effects via ERα. Our studies indicate that targeting this pathway in PAH may provide a promising antiproliferative therapeutic strategy

Stepping Forward With MD: Current Research on Five Common Types

The muscular dystrophies (MDs) encompass a range of genetic diseases characterized primarily by skeletal muscle wasting, with possible weakening of the heart. Clinical manifestations of these diseases have been documented for more than a century; however, the molecular defects that cause MD were only discovered in the last twenty years. Some forms of the disease, including Duchenne muscular dystrophy (DMD) and congenital muscular dystrophy (CMD), result from mutations in genes coding for proteins crucial to muscle cell structure. In these forms of MD, symptoms result from a deficiency of dystrophin or an associated protein in the dystrophin-glycoprotein complex (DGC), a structure that preserves function of normal muscle fibers. Another form of MD, limb-girdle muscular dystrophy (LGMD), is caused by a mutation encoding a protein component of the plasma membrane. Still other forms of the disease exist; fascioscapulohumeral muscular dystrophy (FSHD) and myotonic dystrophy (DM) result from nucleotide repeats and silencer deletions on skeletal muscle genes, respectively. In these forms of MD, symptoms are due to abnormal pre-mRNA splicing. This paper reviews current literature on the molecular basis and therapeutic strategies of five types of MD

Documenting Local History: Using the Library of Congress Site, Primary Sources, and Community Resources for Teaching Social Studies

In the 2011 academic school year, a central Illinois jr. high school and a private university initiated a partnership to create a local history research project. Through a grant from the Library of Congress Teaching with Primary Sources Project at the Federation of Independent Illinois Colleges and Universities, teachers and professors collaborated to identify information for research and design the inquiry’s final product for the project. Through the guidance of their teachers, seventh and eighth grade students accessed the Library of Congress resources and town primary sources for research. Historical inquiry included the identification of the town’s origination and important events that occurred through the years of 1830 to 2012. They gathered data, developed interview questions and interviewed local residents. The students analyzed auditory and visual primary sources to identify the growth of the town through the years and created a video documentary. The documentary continues to be used each year for the teaching and learning of Social Studies

Nonfarm enterprises in rural Ethiopia: improving livelihoods by generating income and smoothing consumption?

In developing countries highly dependent on agriculture, non-farm enterprises (NFEs) are often lauded as income diversification opportunities, helping to smooth income in the farming off-seasons. Using data from the first wave of the Ethiopia Socioeconomic Survey (ESS), a nationally representative survey of rural and small town Ethiopia, we explore the role NFEs play in seasonal income generation, consumption smoothing, and risk mitigation. We find that NFEs are in fact pro-cyclical with agriculture, with the most productive months of NFE operation coinciding with the harvest season and crop sales. This procyclicality appears to be driven by demand-side factors, where increases in community income through crop sales generate higher demand for NFE goods and services. We also find no evidence that households operating NFEs are better able to ward off incidence or duration of food insecurity in the face of shocks, suggesting NFEs do not insure temporally vulnerable households against risks.Keywords: Ethiopia, LSMS, non-farm enterprises, income diversificatio

Clinical audit in farm animal veterinary practice. Part 2: conducting the audit

This article, the second in a two-part series providing practical advice for practitioners on carrying out clinical audits in farm animal practice, focuses on the data collection, analysis and discussion steps of clinical audit. Part 1, which was published in the October issue of In Practice, discussed preparing for and initiating clinical audit in farm animal practice. Both articles are based on findings from a three-year research project looking at the use of clinical audit in farm animal practice. The research included conducting audits using information already in existence in the practice setting, and audits focused on actively collecting information over a period of time in three farm animal practices, and a nationwide survey on the experiences and attitudes of farm animal veterinary surgeons towards clinical audit in the UK. The findings from this work demonstrate that clinical audit is achievable in farm animal practice, with strategic planning, selection of relevant topics and the setting of realistic goals

Clinical audit in farm animal veterinary practice: Part 1: preparing for audit

This article, the first in a two-part series providing practical advice for practitioners on carrying out clinical audits, discusses the preparation and initiation of clinical audit in farm animal practice. In the second article, to be published in a subsequent issue of In Practice, the stages of data collection, analysis and re-audit will be discussed along with some of the facilitators and barriers to conducting clinical audit. Both articles are based on findings from a three-year research project looking at the use of clinical audit in farm animal practice. The research included conducting audits using information already in existence in the practice setting, and audits focused on actively collecting information over a period of time in three farm animal practices, and a nationwide survey on the experiences and attitudes of farm animal veterinary surgeons towards clinical audit in the UK