Summary
Background
Non‐steroidal anti‐inflammatory drugs (NSAIDs) are one of the most frequently involved groups of medicines in hypersensitivity drug reactions. Two mechanisms can induce the ...reaction: immunological (sensitization) due to a specific IgE or T cell response and pharmacological (cyclooxygenase inhibition). The contribution of each of these mechanisms to the reactions is not well known.
Objective
To analyse a large group of subjects with confirmed hypersensitivity reactions to NSAIDs.
Methods
The drugs involved, the clinical entities induced and the time interval between drug intake and appearance of the reaction were studied. In cases where the diagnosis was not confirmed, a drug provocation test was carried out. Atopy status was also assessed with prick test and total IgE in serum.
Results
A total of 659 patients were finally considered to have had hypersensitivity reactions to NSAIDs; 76% had cross‐intolerance (CI) and 24% were selective responders (SR). The most important drugs involved in CI were propionic acid derivatives, in most cases ibuprofen, and in SR pyrazolones. In CI, the most frequent clinical entity was urticaria and angio‐oedema and to a lesser extent airway involvement. The skin and airways were both involved in an important proportion of cases. The most frequent entities in SR were urticaria and/or angio‐oedema followed by anaphylaxis. Atopy was significantly associated in the CI group (P<0.005).
Conclusion and Clinical Relevance
Cutaneous hypersensitivity reactions by CI to NSAIDs are the most frequent entities induced by these compounds. In addition to aspirin, other NSAIDs are taking on a predominant role. Atopy can be a predisposing factor in patients with CI.
Cite this as: I. Doña, N. Blanca‐López, J. A. Cornejo‐García, M. J. Torres, J. J. Laguna, J. Fernández, A. Rosado, C. Rondón, P. Campo, J. A. Agúndez, M. Blanca and G. Canto, Clinical & Experimental Allergy, 2011 (41) 86–95.
The protein kinase R (PKR, also called EIF2AK2) is an interferon-inducible double-stranded RNA protein kinase with multiple effects on cells that plays an active part in the cellular response to ...numerous types of stress. PKR has been extensively studied and documented for its relevance as an antiviral agent and a cell growth regulator. Recently, the role of PKR related to metabolism, inflammatory processes, cancer and neurodegenerative diseases has gained interest. In this review, we summarise and discuss the involvement of PKR in several cancer signalling pathways and the dual role that this kinase plays in cancer disease. We emphasise the importance of PKR as a molecular target for both conventional chemotherapeutics and emerging treatments based on novel drugs, and its potential as a biomarker and therapeutic target for several pathologies. Finally, we discuss the impact that the recent knowledge regarding PKR involvement in metabolism has in our understanding of the complex processes of cancer and metabolism pathologies, highlighting the translational research establishing the clinical and therapeutic potential of this pleiotropic kinase.
Yebes 40m radio telescope is the main and largest observing instrument at Yebes Observatory and it is devoted to Very Long Baseline Interferometry (VLBI) and single dish observations since 2010. It ...has been covering frequency bands between 2 GHz and 90 GHz in discontinuous and narrow windows in most of the cases, to match the current needs of the European VLBI Network (EVN) and the Global Millimeter VLBI Array (GMVA).
Nanocosmos project, a European Union funded synergy grant, opened the possibility to increase the instantaneous frequency coverage to observe many molecular transitions with single tunnings in single dish mode. This reduces the observing time and maximises the output from the telescope.
We present the technical specifications of the recently installed 31.5 - 50GHz (Q band) and 72 - 90.5 GHz (W band) receivers along with the main characteristics of the telescope at these frequency ranges. We have observed IRC+10216, CRL 2688 and CRL 618, which harbour a rich molecular chemistry, to demonstrate the capabilities of the new instrumentation for spectral observations in single dish mode.
The results show the high sensitivity of the telescope in the Q band. The spectrum of IRC+10126 offers a signal to noise ratio never seen before for this source in this band. On the other hand, the spectrum normalised by the continuum flux towards CRL 618 in the W band demonstrates that the 40 m radio telescope produces comparable results to those from the IRAM 30 m radio telescope, although with a smaller sensitivity. The new receivers fulfil one of the main goals of Nanocosmos and open the possibility to study the spectrum of different astrophysical media with unprecedented sensitivity.
Background: Liver biopsy is an invasive technique with associated major complications. There is no information on the validity of five non-invasive indexes based on routinely available parameters, ...estimated and validated in hepatitis C virus (HCV) monoinfected patients, in human immunodeficiency virus (HIV)/HCV coinfected patients. Aim: To validate these predictive models of liver fibrosis in HIV/HCV coinfected patients. Patients: A total of 357 (90%) of 398 patients from five hospitals were investigated, who underwent liver biopsy and who had complete data to validate all of the models considered. Methods: The predictive accuracy of the indexes was tested by measuring areas under the receiver operating characteristic curves. Diagnostic accuracy was calculated by estimating sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values. Results: The models performed better when liver biopsies ⩾15 mm were used as reference. In this setting, the Forns and Wai indexes, models aimed at discriminating significant fibrosis, showed PPV of 94% and 87%, respectively. Using these models, 27–34% of patients could benefit from exclusion of liver biopsy. If both models were applied sequentially, 41% of liver biopsies could be spared. The indexes aimed at predicting cirrhosis achieved NPV of up to 100%. However, they showed very low PPV. Conclusions: The diagnostic accuracy of these models was lower in HIV/HCV coinfected patients than in the validation studies performed in HCV monoinfected patients. However, simple fibrosis tests may render liver biopsy unnecessary in deciding anti-HCV treatment in over one third of patients with HIV infection and chronic hepatitis C.
Since the 1995 discovery of the broad iron K-line emission from the Seyfert galaxy MCG-6-30-15 (ref. 1), broad iron K lines have been found in emission from several other Seyfert galaxies, from ...accreting stellar-mass black holes and even from accreting neutron stars. The iron K line is prominent in the reflection spectrum created by the hard-X-ray continuum irradiating dense accreting matter. Relativistic distortion of the line makes it sensitive to the strong gravity and spin of the black hole. The accompanying iron L-line emission should be detectable when the iron abundance is high. Here we report the presence of both iron K and iron L emission in the spectrum of the narrow-line Seyfert 1 galaxy 1H 0707-495. The bright iron L emission has enabled us to detect a reverberation lag of about 30 s between the direct X-ray continuum and its reflection from matter falling into the black hole. The observed reverberation timescale is comparable to the light-crossing time of the innermost radii around a supermassive black hole. The combination of spectral and timing data on 1H 0707-495 provides strong evidence that we are witnessing emission from matter within a gravitational radius, or a fraction of a light minute, from the event horizon of a rapidly spinning, massive black hole.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The transformation of mechanical energy into electrical signals is the first step in mechanotransduction in the peripheral sensory nervous system and relies on the presence of mechanically gated ion ...channels within specialized sensory organs called mechanoreceptors. Piezo2 is a vertebrate stretch‐gated ion channel necessary for mechanosensitive channels in mammalian cells. Functionally, it is related to light touch, which has been detected in murine cutaneous Merkel cell–neurite complexes, Meissner‐like corpuscles and lanceolate nerve endings. To the best of our knowledge, the occurrence of Piezo2 in human cutaneous mechanoreceptors has never been investigated. Here, we used simple and double immunohistochemistry to investigate the occurrence of Piezo2 in human digital glabrous skin. Piezo2 immunoreactivity was detected in approximately 80% of morphologically and immunohistochemically characterized (cytokeratin 20+, chromogranin A+ and synaptophisin+) Merkel cells. Most of them were in close contact with Piezo2− nerve fibre profiles. Moreover, the axon, but not the lamellar cells, of Meissner's corpuscles was also Piezo2+, but other mechanoreceptors, i.e. Pacinian or Ruffini's corpuscles, were devoid of immunoreactivity. Piezo2 was also observed in non‐nervous tissue, especially the basal keratinocytes, endothelial cells and sweat glands. The present results demonstrate the occurrence of Piezo2 in cutaneous sensory nerve formations that functionally work as slowly adapting (Merkel cells) and rapidly adapting (Meissner's corpuscles) low‐threshold mechanoreceptors and are related to fine and discriminative touch but not to vibration or hard touch. These data offer additional insight into the molecular basis of mechanosensing in humans.
Summary
Background
To date, genetic studies of hypersensitivity reactions to non‐steroidal anti‐inflammatory drugs (NSAIDs) have been carried out mainly in aspirin‐induced asthma and to a lesser ...extent in chronic urticaria, with no studies in patients with acute urticaria (AU), the most common entity induced by these drugs.
Objective
In this work, we analysed the association of common variants of 15 relevant genes encoding both enzymes and receptors from the arachidonic acid (AA) pathway with NSAID‐induced AU.
Methods
Patients were recruited in several Allergy Services that are integrated into the Spanish network RIRAAF, and diagnosed of AU induced by cross‐intolerance (CRI) to NSAIDs. Genotyping was carried out by TaqMan allelic discrimination assays.
Results
A total of 486 patients with AU induced by CRI to NSAIDs and 536 unrelated controls were included in this large Spanish case‐control study. Seven variants from 31 tested in six genes were associated in a discovery study population from Malaga (0.0003 ≤ p‐value ≤ 0.041). A follow‐up analysis in an independent sample from Madrid replicated three of the SNPs from the ALOX15 (rs7220870), PTGDR (rs8004654) and CYSLTR1 (rs320095) genes (1.055x10‐6≤meta‐analysis p‐value ≤ 0.003).
Conclusions and Clinical Relevance
Genetic variants of the AA pathway may play an important role in NSAID‐induced AU. These data may help understand the mechanism underlying this disease.
This paper provides a review of pyrolysis technologies, focusing on reactor designs and companies commercializing these technologies. The renewed interest in pyrolysis is driven by the potential to ...convert lignocellulosic materials into bio-oil and biochar and the use of these intermediates for the production of biofuels, biochemicals, and engineered biochars for environmental services. This review presents slow, intermediate, fast, and microwave pyrolysis as complementary technologies that share some commonalities in their designs. While slow pyrolysis technologies (traditional carbonization kilns) use wood trunks to produce char chunks for cooking, fast pyrolysis systems process small particles to maximize bio-oil yield. The realization of the environmental issues associated with the use of carbonization technologies and the technical difficulties of operating fast pyrolysis reactors using sand as the heating medium and large volumes of carrier gas, as well as the problems with refining the resulting highly oxygenated oils, are forcing the thermochemical conversion community to rethink the design and use of these reactors. Intermediate pyrolysis reactors (also known as converters) offer opportunities for the large-scale balanced production of char and bio-oil. The capacity of these reactors to process forest and agricultural wastes without much preprocessing is a clear advantage. Microwave pyrolysis is an option for modular small autonomous devices for solid waste management. Herein, the evolution of pyrolysis technology is presented from a historical perspective; thus, old and new innovative designs are discussed together.
The microscopic environment inside a metazoan organism is highly crowded. Whether individual cells can tailor their behavior to the limited space remains unclear. In this study, we found that cells ...measure the degree of spatial confinement by using their largest and stiffest organelle, the nucleus. Cell confinement below a resting nucleus size deforms the nucleus, which expands and stretches its envelope. This activates signaling to the actomyosin cortex via nuclear envelope stretch-sensitive proteins, up-regulating cell contractility. We established that the tailored contractile response constitutes a nuclear ruler-based signaling pathway involved in migratory cell behaviors. Cells rely on the nuclear ruler to modulate the motive force that enables their passage through restrictive pores in complex three-dimensional environments, a process relevant to cancer cell invasion, immune responses, and embryonic development.
This paper describes the reliable determination of progesterone (P4) in undiluted saliva making use of a disposable amperometric immunosensors implemented on low-cost and portable device/potentiostat ...constructed with commercial-off-the-shelf (COTS) components. The immunosensor allows the fast (45 min), selective and sensitive determination (5 pg mL−1 LOD) of P4 using amperometry in stirred solutions. The immunosensor was coupled to the COTS-based potentiostat and amperometry was made into drops of quiescent solutions. No significant differences were apparent between the analytical performance achieved with the immunosensor for P4 using both a conventional and the COST-based potentiostats. The practical applicability of the immunosensor coupled with the COTS-based potentiostat was demonstrated by determining the endogenous P4 content in different undiluted saliva samples with highly variable endogenous contents of the target hormone. The obtained results were in good agreement with those provided by the conventional ELISA methodology and with the contents reported in the literature for samples with similar characteristics. This validated the combined device for the reliable and minimally invasive determination of the target hormone involving a very simple protocol and taking only 45 min.
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•Reliable determination of progesterone (P4) in undiluted saliva with a disposable immunosensor.•Portable device/potentiostat constructed with commercial-off-the-shelf (COTS) components.•Fast (45 min) and sensitive determination of P4 using amperometry in stirred solutions or drops of quiescent solutions.•Determination of endogenous P4 in saliva with highly variable contents of the target hormone.
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