Calcitonin gene-related peptide (CGRP) and its receptor components in human and rat spinal trigeminal nucleus and spinal cord at C1-level

<p>Abstract</p> <p>Background</p> <p>Calcitonin gene-related peptide (CGRP) has a key role in migraine pathophysiology and is associated with activation of the trigeminovascular system. The trigeminal ganglion, storing CGRP and its receptor components, projects peripheral to the intracranial vasculature and central to regions in the brainstem with Aδ- and C-fibers; this constitutes an essential part of the pain pathways activated in migraine attacks. Therefore it is of importance to identify the regions within the brainstem that processes nociceptive information from the trigeminovascular system, such as the spinal trigeminal nucleus (STN) and the C1-level of the spinal cord. Immunohistochemistry was used to study the distribution and relation between CGRP and its receptor components - calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1 (RAMP1) - in human and rat STN and at the C1-level, using a set of newly well characterized antibodies. In addition, double-stainings with CGRP and myelin basic protein (MBP, myelin), synaptophysin (synaptic vesicles) or IB4 (C-fibers in general) were performed.</p> <p>Results</p> <p>In the STN, the highest density of CGRP immunoreactive fibers were found in a network around fiber bundles in the superficial laminae. CLR and RAMP1 expression were predominately found in fibers in the spinal trigeminal tract region, with some fibers spanning into the superficial laminae. Co-localization between CGRP and its receptor components was not noted. In C1, CGRP was expressed in fibers of laminae I and II. The CGRP staining was similar in rat, except for CGRP positive neurons that were found close to the central canal. In C1, the receptor components were detected in laminae I and II, however these fibers were distinct from fibers expressing CGRP as verified by confocal microscopy.</p> <p>Conclusions</p> <p>This study demonstrates the detailed expression of CGRP and its receptor components within STN in the brainstem and in the spinal cord at C1-level, and shows the possibility of CGRP acting postjunctionally in these areas putatively involved in primary headaches.</p

Strength and hypertrophy responses to constant and decreasing rest intervals in trained men using creatine supplementation

<p>Abstract</p> <p>Background</p> <p>The purpose of the current study was to compare strength and hypertrophy responses to resistance training programs that instituted constant rest intervals (CI) and decreasing rest intervals (DI) between sets over the course of eight weeks by trained men who supplemented with creatine monohydrate (CR).</p> <p>Methods</p> <p>Twenty-two recreationally trained men were randomly assigned to a CI group (n = 11; 22.3 ± 1 years; 77.7 ± 5.4 kg; 180 ± 2.2 cm) or a DI group (n = 11; 22 ± 2.5 years; 75.8 ± 4.9 kg; 178.8 ± 3.4 cm). Subjects in both groups supplemented with CR; the only difference between groups was the rest interval instituted between sets; the CI group used 2 minutes rest intervals between sets and exercises for the entire 8-weeks of training, while the DI group started with a 2 minute rest interval the first two weeks; after which the rest interval between sets was decreased 15 seconds per week (i.e. 2 minutes decreasing to 30 seconds between sets). Pre- and post-intervention maximal strength for the free weight back squat and bench press exercises and isokinetic peak torque were assessed for the knee extensors and flexors. Additionally, muscle cross-sectional area (CSA) of the right thigh and upper arm was measured using magnetic resonance imaging.</p> <p>Results</p> <p>Both groups demonstrated significant increases in back squat and bench press maximal strength, knee extensor and flexor isokinetic peak torque, and upper arm and right thigh CSA from pre- to post-training (p ≤ 0.0001); however, there were no significant differences between groups for any of these variables. The total volume for the bench press and back squat were significantly greater for CI group versus the DI group.</p> <p>Conclusions</p> <p>We report that the combination of CR supplementation and resistance training can increase muscular strength, isokinetic peak torque, and muscle CSA, irrespective of the rest interval length between sets. Because the volume of training was greater for the CI group versus the DI group, yet strength gains were similar, the creatine supplementation appeared to bolster adaptations for the DI group, even in the presence of significantly less volume. However, further research is needed with the inclusion of a control group not receiving supplementation combined and resistance training with decreasing rest intervals to further elucidate such hypotheses.</p

Mercury exposure, malaria, and serum antinuclear/antinucleolar antibodies in amazon populations in Brazil: a cross-sectional study

BACKGROUND: Mercury is an immunotoxic metal that induces autoimmune disease in rodents. Highly susceptible mouse strains such as SJL/N, A.SW, B10.S (H-2(s)) develop multiple autoimmune manifestations after exposure to inorganic mercury, including lymphoproliferation, elevated levels of autoantibodies, overproduction of IgG and IgE, and circulating immune complexes in kidney and vasculature. A few studies have examined relationships between mercury exposures and adverse immunological reactions in humans, but there is little evidence of mercury-associated autoimmunity in humans. METHODS: To test the immunotoxic effects of mercury in humans, we studied communities in Amazonian Brazil with well-characterized exposures to mercury. Information was collected on diet, mercury exposures, demographic data, and medical history. Antinuclear and antinucleolar autoantibodies (ANA and ANoA) were measured by indirect immunofluorescence. Anti-fibrillarin autoantibodies (AFA) were measured by immunoblotting. RESULTS: In a gold mining site, there was a high prevalence of ANA and ANoA: 40.8% with detectable ANoA at ≥1:10 serum dilution, and 54.1% with detectable ANA (of which 15% had also detectable ANoA). In a riverine town, where the population is exposed to methylmercury by fish consumption, both prevalence and levels of autoantibodies were lower: 18% with detectable ANoA and 10.7% with detectable ANA. In a reference site with lower mercury exposures, both prevalence and levels of autoantibodies were much lower: only 2.0% detectable ANoA, and only 7.1% with detectable ANA. In the gold mining population, we also examined serum for AFA in those subjects with detectable ANoA (≥1:10). There was no evidence for mercury induction of this autoantibody. CONCLUSIONS: This is the first study to report immunologic changes, indicative of autoimmune dysfunction in persons exposed to mercury, which may also reflect interactions with infectious disease and other factors

One-loop effective actions and higher spins

The idea we advocate in this paper is that the one-loop effective action of a free (massive) field theory coupled to external sources (via conserved currents) contains complete information about the classical dynamics of such sources. We show many explicit examples of this fact for (scalar and fermion) free field theories in various dimensions d = 3,4,5,6 coupled to (bosonic, completely symmetric) sources with a number of spins. In some cases we also provide compact formulas for any dimension. This paper is devoted to two-point correlators, so the one-loop effective action we construct contains only the quadratic terms and the relevant equations of motion for the sources we obtain are the linearized ones

Spatial Evaluation and Modeling of Dengue Seroprevalence and Vector Density in Rio de Janeiro, Brazil

Dengue is a major public health problem in many tropical regions of the world, including Brazil, where Aedes aegypti is the main vector. We present a household study that combines data on dengue fever seroprevalence, recent dengue infection, and vector density, in three neighborhoods of Rio de Janeiro, Brazil, during its most devastating dengue epidemic to date. This integrated entomological–serological survey showed evidence of silent transmission even during a severe epidemic. Also, past exposure to dengue virus was highly associated with age and living in areas of high movement of individuals and social/commercial activity. No association was observed between household infestation index and risk of dengue infection in these areas. Our findings are discussed in the light of current theories regarding transmission thresholds and relative role of mosquitoes and humans as vectors of dengue viruses

Structure of a lectin from Canavalia gladiata seeds: new structural insights for old molecules

<p>Abstract</p> <p>Background</p> <p>Lectins are mainly described as simple carbohydrate-binding proteins. Previous studies have tried to identify other binding sites, which possible recognize plant hormones, secondary metabolites, and isolated amino acid residues. We report the crystal structure of a lectin isolated from <it>Canavalia gladiata </it>seeds (CGL), describing a new binding pocket, which may be related to pathogen resistance activity in ConA-like lectins; a site where a non-protein amino-acid, α-aminobutyric acid (Abu), is bound.</p> <p>Results</p> <p>The overall structure of native CGL and complexed with α-methyl-mannoside and Abu have been refined at 2.3 Å and 2.31 Å resolution, respectively. Analysis of the electron density maps of the CGL structure shows clearly the presence of Abu, which was confirmed by mass spectrometry.</p> <p>Conclusion</p> <p>The presence of Abu in a plant lectin structure strongly indicates the ability of lectins on carrying secondary metabolites. Comparison of the amino acids composing the site with other legume lectins revealed that this site is conserved, providing an evidence of the biological relevance of this site. This new action of lectins strengthens their role in defense mechanisms in plants.</p

Distribution Patterns of Infection with Multiple Types of Human Papillomaviruses and Their Association with Risk Factors

Background: Infection with multiple types of human papillomavirus (HPV) is one of the main risk factors associated with the development of cervical lesions. In this study, cervical samples collected from 1, 810 women with diverse sociocultural backgrounds, who attended to their cervical screening program in different geographical regions of Colombia, were examined for the presence of cervical lesions and HPV by Papanicolau testing and DNA PCR detection, respectively. Principal Findings: The negative binomial distribution model used in this study showed differences between the observed and expected values within some risk factor categories analyzed. Particularly in the case of single infection and coinfection with more than 4 HPV types, observed frequencies were smaller than expected, while the number of women infected with 2 to 4 viral types were higher than expected. Data analysis according to a negative binomial regression showed an increase in the risk of acquiring more HPV types in women who were of indigenous ethnicity (+37.8%), while this risk decreased in women who had given birth more than 4 times (-31.1%), or were of mestizo (-24.6%) or black (-40.9%) ethnicity. Conclusions: According to a theoretical probability distribution, the observed number of women having either a single infection or more than 4 viral types was smaller than expected, while for those infected with 2-4 HPV types it was larger than expected. Taking into account that this study showed a higher HPV coinfection rate in the indigenous ethnicity, the role of underlying factors should be assessed in detail in future studies.This project was funded by Asociacion Investigacion Solidaria SADAR, Caja Navarra (Navarra, Spain) and the Spanish Agency for International Development Cooperation (AECID) (Project 08-CAP2-0609)

Impact of a pharmaceutical care programme on health-related quality of life among women with epilepsy: a randomised controlled trial (IPHIWWE study)

This paper was presented in part at the II Congreso Colombiano de Atención Farmacéutica, Medellín, Colombia, September 27, 2013.Background: Epilepsy is a complex chronic disorder which affects health-related quality of life (HRQOL), especially in women. Pharmaceutical care (PC) allows direct intervention between the pharmacist, the patient and the other healthcare team members to optimise treatments in order to reduce negative outcomes related to medication and contribute to improving HRQOL. The aim of the study was to establish the impact of the application of a pharmaceutical care programme on the HRQOL of women with epilepsy.Methods: This study is a pragmatic randomised controlled trial involving women with epilepsy (WWE) over 18 years of age. The intervention group (IG) received a pharmaceutical care programme consisting of medication review follow-up according to Dáder’s method, health education and therapeutic drug monitoring of anticonvulsants. The impact was assessed by changes in seizure frequency, in the self-administered questionnaires (the QOLIE-31, Liverpool AEP, CES-D, Haynes-Sackett test and Moriski-Green test) and between the first interview and the one at the end of six months of follow-up. A Student’s t-test was performed to compare the final QOLIE-31 score between groups and a paired Student’s t-test was used to determine the change in each group between the start and the end of follow-up.Results: One hundred eighty-two WWE entered the study and 144 (79.1%) completed it. The t-test for comparing the final QOLIE-31 scores between groups yielded a t = −2.166 and confidence interval (CI) (95%): −10.125; −0.4625, p-value =0.0319. The change (Δ) in the QOLIE-31 score for the IG was 12.45 points (p-value <0.001) and for the control group it was 2.61 (p-value =0.072). With 10.7 as the minimally important change we found a relative risk of 2.17 (CI: 1.37; 3.43) and a number needed to treat (NNT) of 3.5.Conclusions: The study demonstrated that the application of a pharmaceutical care programme significantly improves HRQOL in WWE. The NNT we found allows a recommendation to implement the PC programme for the additional benefit that would be obtained in patients’ HRQOL.This study was funded by a competitive investigator grant award from the Universidad Nacional de Colombia (Colombia) - Research Division of Bogotá (ref: 202010011419 Quipu Code)