Obesity and altered arterial structure in young women with micropolycystic ovary syndrome

OBJETIVO: comparar os fatores ecográficos de risco cardiovascular em pacientes obesas e não obesas, com síndrome dos ovários micropolicísticos (SOMP). MÉTODOS: foram incluídas 30 pacientes obesas com SOMP (Índice de massa corporal, IMC>30 kg/m²) e 60 não obesas (IMC<30 kg/m²), com idade entre 18 e 35 anos neste estudo transversal. Foram avaliados: a dilatação mediada por fluxo (DMF) da artéria braquial, espessura íntima-média da artéria carótida (IMT), o índice de rigidez da artéria carótida (&#946;), as medidas antropométricas, pressão sanguínea sistólica (PAS) e diastólica (PAD). As mulheres estavam sem nenhum tratamento prévio e nenhuma delas apresentava qualquer comorbidade (além da SOMP e/ou da obesidade).Na análise estatística, foram utilizados os testes t não-pareado ou de Mann-Whitney. RESULTADOS: as pacientes obesas com SOMP apresentaram maior peso em relação às não obesas (92,1±11,7 kg versus 61,4±10,7 kg, p<0,0001), bem como a medida da cintura que também, foi mais elevada nas pacientes obesas (105,0±10,4 cm versus 78,5±9,8 cm, p<0,0001). A PAS das pacientes obesas foi superior quando comparadas às não obesas (126,1±10,9 mmHg versus 115,8±9,0 mmHg, p<0,0001) e a IMT também foi maior nas obesas (0,51±0,07 mm versus 0,44±0,09 mm, p<0,0001). Não houve diferença entre os grupos quanto à dilatação mediada por fluxo (DMF) da artéria braquial ou ao índice de rigidez da artéria carótida (&#946;). CONCLUSÕES: a obesidade em portadoras jovens de SOMP está associada a níveis pressóricos mais elevados e à alteração da estrutura arterial, representada pela maior espessura íntima-média da artéria carótida.PURPOSE: to compare echographical cardiovascular risk factors between obese and non-obese patients with micropolycystic ovarian syndrome (MPOS). METHODS: in this transversal study, 30 obese (Body Mass Index, BMI>30 kg/m²) and 60 non-obese (BMI<30 kg/m²) MPOS patients, aging between 18 and 35 years old, were included. The following variables were measured: flow-mediated dilatation (FMD) of the brachial artery, thickness of the intima-media of the carotid artery (IMT), anthropometric data, systolic arterial pressure (SAP) and diastolic arterial pressure (DAP). The women had no previous medical treatment and no comorbidity besides MPOS and obesity. For statistical analysis, the non-paired tand Mann-Whitney's tests were used. RESULTS: obese weighted more than non-obese patients (92.1±11.7 kg versus 61.4±10.7 kg, p<0.0001) and had a larger waist circumference (105.0±10.4 cm versus 78.5±9.8 cm, p<0.0001). The SBP of obese patients was higher than that of the non-obese ones (126.1±10.9 mmHg versus 115.8±9.0 mmHg, p<0.0001) and the IMT was also bigger (0.51±0.07 mm versus 0.44±0.09 mm, p<0.0001). There was no significant difference between the groups as to FMD and carotid rigidity index (&#946;). CONCLUSIONS: obesity in young women with MPOS is associated with higher blood pressure and alteration of arterial structure, represented by a thicker intima-media of the carotid artery

ADDovenom: Thermostable Protein-Based ADDomer Nanoparticles as New Therapeutics for Snakebite Envenoming

Snakebite envenoming can be a life-threatening medical emergency that requires prompt medical intervention to neutralise the effects of venom toxins. Each year up to 138,000 people die from snakebites and threefold more victims suffer life-altering disabilities. The current treatment of snakebite relies solely on antivenom—polyclonal antibodies isolated from the plasma of hyperimmunised animals—which is associated with numerous deficiencies. The ADDovenom project seeks to deliver a novel snakebite therapy, through the use of an innovative protein-based scaffold as a next-generation antivenom. The ADDomer is a megadalton-sized, thermostable synthetic nanoparticle derived from the adenovirus penton base protein; it has 60 high-avidity binding sites to neutralise venom toxins. Here, we outline our experimental strategies to achieve this goal using state-of-the-art protein engineering, expression technology and mass spectrometry, as well as in vitro and in vivo venom neutralisation assays. We anticipate that the approaches described here will produce antivenom with unparalleled efficacy, safety and affordability

A transcriptomic analysis of gene expression in the venom gland of the snake Bothrops alternatus (urutu)

<p>Abstract</p> <p>Background</p> <p>The genus <it>Bothrops </it>is widespread throughout Central and South America and is the principal cause of snakebite in these regions. Transcriptomic and proteomic studies have examined the venom composition of several species in this genus, but many others remain to be studied. In this work, we used a transcriptomic approach to examine the venom gland genes of <it>Bothrops alternatus</it>, a clinically important species found in southeastern and southern Brazil, Uruguay, northern Argentina and eastern Paraguay.</p> <p>Results</p> <p>A cDNA library of 5,350 expressed sequence tags (ESTs) was produced and assembled into 838 contigs and 4512 singletons. BLAST searches of relevant databases showed 30% hits and 70% no-hits, with toxin-related transcripts accounting for 23% and 78% of the total transcripts and hits, respectively. Gene ontology analysis identified non-toxin genes related to general metabolism, transcription and translation, processing and sorting, (polypeptide) degradation, structural functions and cell regulation. The major groups of toxin transcripts identified were metalloproteinases (81%), bradykinin-potentiating peptides/C-type natriuretic peptides (8.8%), phospholipases A₂(5.6%), serine proteinases (1.9%) and C-type lectins (1.5%). Metalloproteinases were almost exclusively type PIII proteins, with few type PII and no type PI proteins. Phospholipases A₂were essentially acidic; no basic PLA₂were detected. Minor toxin transcripts were related to L-amino acid oxidase, cysteine-rich secretory proteins, dipeptidylpeptidase IV, hyaluronidase, three-finger toxins and ohanin. Two non-toxic proteins, thioredoxin and double-specificity phosphatase Dusp6, showed high sequence identity to similar proteins from other snakes. In addition to the above features, single-nucleotide polymorphisms, microsatellites, transposable elements and inverted repeats that could contribute to toxin diversity were observed.</p> <p>Conclusions</p> <p><it>Bothrops alternatus </it>venom gland contains the major toxin classes described for other <it>Bothrops </it>venoms based on trancriptomic and proteomic studies. The predominance of type PIII metalloproteinases agrees with the well-known hemorrhagic activity of this venom, whereas the lower content of serine proteases and C-type lectins could contribute to less marked coagulopathy following envenoming by this species. The lack of basic PLA₂agrees with the lower myotoxicity of this venom compared to other <it>Bothrops </it>species with these toxins. Together, these results contribute to our understanding of the physiopathology of envenoming by this species.</p

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Snake venomics of crotalus tigris: the minimalist toxin arsenal of the deadliest neartic rattlesnake venom: evolutionary clues for generating a pan-specific antivenom against crotalid type II venoms

artículo (arbitrado)-- Universidad de Costa Rica, Instituto de Investigaciones Clodomiro Picado. 2012. This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Proteome Research, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work seehttp://pubs.acs.org/doi/abs/10.1021/pr201021dWe report the proteomic and antivenomic characterization of Crotalus tigris venom. This venom exhibits the highest lethality for mice among rattlesnakes and the simplest toxin proteome reported to date. The venom proteome of C. tigris comprises 7–8 gene products from 6 toxin families: the presynaptic β-neurotoxic heterodimeric PLA2, Mojave toxin, and two serine proteinases comprise, respectively, 66% and 27% of the C. tigris toxin arsenal, whereas a VEGF-like protein, a CRISP molecule, a medium-sized disintegrin, and 1–2 PIII-SVMPs, each represents 0.1–5% of the total venom proteome. This toxin profile really explains the systemic neuro- and myotoxic effects observed in envenomated animals. In addition, we found that venom lethality of C. tigris and other North American rattlesnake type II venoms correlates with the concentration of Mojave toxin A subunit, supporting the view that the neurotoxic venom phenotype of crotalid type II venoms may be described as a single-allele adaptation. Our data suggest that the evolutionary trend towards neurotoxicity, which has been also reported for the South American rattlesnakes, may have resulted by paedomorphism. The ability of an experimental antivenom to effectively immunodeplete proteins from the type II venoms of C. tigris, C. horridus, C. oreganus helleri, C. scutulatus scutulatus, and S. catenatus catenatus, indicated the feasibility of generating a pan-American anti-Crotalus type II antivenom, suggested by the identification of shared evolutionary trends among South American and North American Crotalus.Financed by grants BFU2010-17373 (from the Ministerio de Ciencia e Innovación, Madrid, Spain), CRUSA-CSIC (project 2009CR0021), and PROMETEO/2010/005 from the Generalitat Valenciana (Valencia, Spain), NIH/VIPER resource grant (#5 P40 RR018300-09), and Texas A&M University-Kingsville.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP