1,720,964 research outputs found
Targeting kinin receptors for the treatment of neurological diseases
No full textKinins (bradykinin, kallidin and their active metabolites) are peptide autacoids with established functions in
cardiovascular homeostasis, contraction and relaxation of smooth muscles, inflammation and nociception. They are
believed to play a role in disease states like asthma, allergies, rheumatoid arthritis, cancer, diabetes, endotoxic and
pancreatic shock, and to contribute to the therapeutic effects of ACE inhibitors in cardiovascular diseases. Although kinins
are also neuromediators in the central nervous system, their involvement in neurological diseases has not been intensively
investigated thus far. This review analyzes the potential of central kinin receptors as therapeutic targets for neurological
disorders. Initial data highlight potential roles for B1 receptor antagonists as antiepileptic agents, and for B2 receptor
antagonists (and/or B1 agonists) in the treatment of stroke. Functional B1 receptors located on T-lymphocytes and on the
blood brain-barrier are also putative targets for the management of multiple sclerosis. However, successful elucidation of
the therapeutic value of these new pharmacological approaches will require refinement of our knowledge on the
physiology and cellular localization of central kinin receptors
Increases of spinal kinin receptor binding sites in two rat models of insulin resistance
No full textAn autoradiographic study was conducted to determine whether kinin receptors are altered in the rat spinal cord in two experimental
models of chronic hyperglycemia and insulin resistance. Sprague-Dawley rats were given 10% d-glucose in their drinking water alone or
with insulin (9 mU/kg/min with osmotic pumps) for 4 weeks. Both groups and control rats were treated either with a normal chow diet
or with an alpha-lipoic acid-supplemented diet as antioxidant therapy. After 4 weeks of treatment, glycemia, insulinemia, blood pressure,
insulin resistance index, the production of superoxide anion in the aorta and the density of B1 receptor binding sites in the dorsal horn were
significantly increased in the two models. These effects were prevented or attenuated by alpha-lipoic acid. In contrast, B2 receptor binding
sites of most spinal cord laminae were increased in the glucose group only and were not affected by alpha-lipoic acid. Results show that
chronic hyperglycemia associated with insulin resistance increases B1 and B2 receptor binding sites in the rat spinal cord through distinct
mechanisms, including the oxidative stress for the B1 receptor
Autoradiographic analysis of rat brain kinin B-1 and B-2 receptors: Normal distribution and alterations induced by epilepsy
No full textKindling-induced seizures constitute an experimental model of human temporal lobe epilepsy that is associated with changes in the expression of several inflammatory proteins and/or their receptors in distinct brain regions. In the present study, alterations of kinin receptors in the brain of amygdaloid-kindled rats were assessed by means of in vitro autoradiography, using 125I-labeled 3-4 hydroxyphenyl-propionyl-desArg9-D-Arg°-[Hyp3, Thi5, D-Tic7, Oic8]-bradykinin (B1 receptors) and 125I-labeled 3-4 hydroxyphenyl-propionyl-D-Arg°[Hyp3, Thi5, D-Tic7, Oic8]-bradykinin (B2 receptors) as ligands. Results demonstrate that B2 receptors are widely distributed throughout the brain of control rats. The highest densities were observed in lateral septal nucleus, median preoptic nucleus, dentate gyrus, amygdala, spinal trigeminal nucleus, mediovestibular nucleus, inferior cerebellar peduncles, and in most of cortical regions (0.81-1.4 fmol/mg tissue). In contrast, very low densities of B1 receptors were detected in all analyzed areas from control rats (0.18-0.26 fmol/mg tissue). When assessed in kindled rats, specific binding sites for B2 receptors were significantly decreased (41 to 76%) in various brain areas. Conversely, B1 receptor binding sites were markedly increased in kindled rats, especially in hippocampus (CA2 ≅ CA1 ≅ CA3), Amy and entorhinal, peririnal/piriform, and occipital cortices (152-258%). Data show for the first time that kindling-induced epilepsy results in a significant decline of B2 receptor binding sites, accompanied by a striking increase of B1 receptor labeling in the rat brain. An altered balance between B1 and B2 receptor populations may play a pivotal role in the onset and/or maintenance of epilepsy. © 2003 Wiley-Liss, Inc
Expression of kinin B-1 receptors in the spinal cord of streptozotocin-diabetic rat
No full textPrevious studies have reported cardiovascular and nociceptive responses
after intrathecal injection of kinin B1 receptor (B1R) agonists
in the model of streptozotocin (STZ)-diabetic rat (diabetic).
The aim of this study was to measure the early up-regulation of
B1R binding sites andmRNA in the thoracic spinal cord of diabetic
and control rats. Data show signi¢cant increases of speci¢c B1R
binding sites in the dorsal horn of diabetic rats 2 days (+315%), 7
days (+303%) and 21days (+181%) after STZ treatment. Levels of
mRNAwere signi¢cantly increased (+68%) at 2 and 7 days but not
at 21days.These data bring the ¢rstmolecular evidence for an early
up-regulation of B1R in the spinal cord of diabetic rat. NeuroReport
15:2463^2466 c 2004 LippincottWilliams &Wilkins
Induction of B<sub>1</sub> bradykinin receptors in the kindled brain
No full textThe data suggest that the B1 BK receptors may play a role in the physiopathology of epilepsy, and may represent a new interesting therapeutic target. Tools are available to challenge this idea both pharmacologically (using B1 and B2 receptor antagonists) and genetically (using B1 and B2 receptor knock-outs)
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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