Activated status of basophils in chronic urticaria leads to interleukin-3 hyper-responsiveness and enhancement of histamine release induced by anti-IgE stimulus

Background Basophils and mast cells are the main target cells in chronic idiopathic urticaria (CIU). Besides the basopenia, intrinsic defects of the anti-IgE cross-linking signalling pathway of basophils have been described in CIU. Objectives We sought to investigate the profile of expression of activation markers on basophils of patients with CIU and to explore the effect of interleukin (IL)-3 priming upon anti-IgE cross-linking stimuli through expression of activation markers and basophil histamine releasability. Methods Evaluation of the surface expression of Fc epsilon RI alpha, CD63, CD203c and CD123 on whole blood basophils of patients with CIU undergoing autologous serum skin test (ASST) was performed by flow cytometry. The effect of pretreatment with IL-3 in the anti-IgE response was analysed by the expression of basophil activation markers and histamine release using enzyme-linked immunosorbent assay. Results Blood basophils of patients with CIU were reduced in number and displayed increased surface expression of Fc epsilon RI alpha, which was positively correlated with the IgE serum levels. Upregulation of expression of both surface markers CD203c and CD63 was verified on basophils of patients with CIU, regardless of ASST response. High expression of IL-3 receptor on basophils was detected only in ASST+ patients with CIU. Pretreatment with IL-3 upregulated CD203c expression concomitantly with the excreting function of blood basophils and induced a quick hyper-responsiveness to anti-IgE cross-linking on basophils of patients with CIU compared with healthy controls. Conclusions Basophils of patients with CIU showed an activated profile, possibly due to an in vivo priming. Functionally, basophils have high responsiveness to IL-3 stimulation, thereby suggesting that defects in the signal transduction pathway after IgE cross-linking stimuli are recoverable in subjects with chronic urticaria.

Relation between Videofluoroscopy of the Esophagus and the Quality of Esophageal Speech

The goal of the current study was to compare the quality of esophageal speech and voice to videofluoroscopic features of the esophagus and pharyngoesophageal (PE) segment. The speech and voice characteristics of 30 laryngectomized patients were rated by 5 speech-language pathologists. Based on these ratings, patients were divided into 3 categories: fluent (n = 9), moderately fluent (n = 10) and nonfluent (n = 11). Videofluoroscopy of the PE region was then performed during both swallowing and voice production. An insufflation test and percutaneous pharyngeal plexus block were required in 9 patients to determine the etiology of poor esophageal voice production. The strongest videofluoroscopic indicators of nonfluent speakers were: (1) small or absent air reservoir and (2) lack of a vibrating PE segment. Fluent speakers presented with shorter PE segments (1.17 mm) compared to moderately fluent speakers (17.1-29.9 mm). Perceptually, fluent speakers presented with a predominantly rough vocal quality. In contrast, moderately fluent speakers presented with a tense quality. In addition, stoma blast noise was reduced in fluent speakers. Videofluoroscopic findings highly correlated with the quality of esophageal speech. Copyright (C) 2009 S. Karger AG, Basel

Enhancement of diagnostic efficiency by a gamma interferon release assay for pulmonary tuberculosis

This study was designed to examine the use of the QuantiFERON-TB Gold assay as an aid in the diagnosis of active pulmonary tuberculosis (TB) in Brazilian patients. Using the receiver operating characteristic curve, the cutoff was adjusted to >= 0.20 IU/ml. The sensitivity increased to 86%, with 100% specificity. All TB patients with negative sputum smear microscopy and negative culture results were positive using this test.

Hydrogen sulfide augments neutrophil migration through enhancement of adhesion molecule expression and prevention of CXCR2 internalization: Role of ATP-sensitive potassium channels

In this study, we have addressed the role of H2S in modulating neutrophil migration in either innate (LPS-challenged naive mice) or adaptive (methylated BSA (mBSA)-challenged immunized mice) immune responses. Treatment of mice with H S synthesis inhibitors, DL-propargylglycine (PAG) or beta-cyanoalanine, reduced neutrophil migration induced by LPS or methylated BSA (mBSA) into the peritoneal cavity and by mBSA into the femur/tibial joint of immunized mice. This effect was associated with decreased leukocyte rolling, adhesion, and P-selectin and ICAM-1 expression on endothelium. Predictably, treatment of animals with the H2S donors, NaHS or Lawesson`s reagent, enhanced these parameters. Moreover, the NaHS enhancement of neutrophil migration was not observed in ICAM-1-deficient mice. Neither PAG nor NaHS treatment changed LPS-induced CD18 expression on neutrophils, nor did the LPS- and mBSA-induced release of neutrophil chemoattractant mediators TNF-alpha, keratinocyte-derived chemokine, and LTB4. Furthermore, in vitro MIP-2-induced neutrophil chemotaxis was inhibited by PAG and enhanced by NaHS treatments. Accordingly, MIP-2-induced CXCR2 internalization was enhanced by PAG and inhibited by NaHS treatments. Moreover, NaHS prevented MIP-2-induced CXCR2 desensitization. The PAG and NaHS effects correlated, respectively, with the enhancement and inhibition of MIP-2-induced G protein-coupled receptor kinase 2 expression. The effects of NaHS on neutrophil migration both in vivo and in vitro, together with CXCR2 internalization and G protein-coupled receptor kinase 2 expression were prevented by the ATP-sensitive potassium (K-ATP(+)) channel blocker, glybenclamide. Conversely, diazoxide, a K-ATP(+) channel opener, increased neutrophil migration in vivo. Together, our data suggest that during the inflammatory response, H`S augments neutrophil adhesion and locomotion, by a mechanism dependent on K-ATP(+) channels.

Neutrophil activation induced by ArtinM: Release of inflammatory mediators and enhancement of effector functions

The D-mannose binding lectin ArtinM from Artocarpus integrifolia, previously known as KM+ and artocarpin. is considered a stimulant of Th1-type immunity, which is able to confer resistance to some intracellular pathogens. In addition, ArtinM induces neutrophil migration by haptotaxis through simultaneous interactions of its carbohydrate recognition domains (CRDs) with glycans expressed on the extracellular matrix and the neutrophil surface. In the present study, we have expanded the characterization of ArtinM as a neutrophil activator. Exposure of neutrophils to ArtinM for 15 min resulted in tyrosine phosphorylation of intracellular proteins, a process that was selectively inhibited by D-mannose or mannotriose. Shortly after stimulation, neutrophils secreted high levels of LTB(4) and underwent shedding of L-selectin from their surface. Exposure to ArtinM enhanced neutrophil functions, such as respiratory burst and zymozan and Listeria monocytogenes phagocytosis. In addition, ArtinM-stimulated neutrophils displayed increased CXCL-8 secretion and TLR2 gene transcription. These results demonstrate that ArtinM is able to induce potent neutrophil activation, a feature that should be strongly considered in the assessment of the lectin capacity to confer resistance against infections. (C) 2009 Elsevier B.V. All rights reserved.

Speech intelligibility with and without noise in individuals exposed to electronic music

Audiometry is the main way with which hearing is evaluated, because it is a universal and standardized test. Speech tests are difficult to standardize due to the variables involved, their performance in the presence of competitive noise is of great importance. Aim: To characterize speech intelligibility in silence and in competitive noise from individuals exposed to electronically amplified music. Material and Method: It was performed with 20 university students who presented normal hearing thresholds. The speech recognition rate (SRR) was performed after fourteen hours of sound rest after the exposure to electronically amplified music and once again after sound rest, being studied in three stages: without competitive noise, in the presence of Babble-type competitive noise, in monotic listening, in signal/ noise ratio of + 5 dB and with the signal/ noise ratio of 5 dB. Results: There was greater damage in the SRR after exposure to the music and with competitive noise, and as the signal/ noise ratio decreases, the performance of individuals in the test also decreased. Conclusion: The inclusion of competitive noise in the speech tests in the audiological routine is important, because it represents the real disadvantage experienced by individuals in daily listening.

Objective Assessment of Internal Nasal Dimensions and Speech Resonance in Individuals With Repaired Unilateral Cleft Lip and Palate After Rhinoseptoplasty

The objective of the current study was to analyze the effects of rhinoseptoplasty on internal nasal dimensions and speech resonance of individuals with unilateral cleft lip and palate, estimated by acoustic rhinometry and nasometry, respectively. Twenty-one individuals (aged 15-46 years) with previously repaired unilateral cleft lip and palate were analyzed before (PRE), and 6 to 9 (POST1) and 12 to 18 months (POST2) after surgery. Acoustic rhinometry was used to measure the cross-sectional areas (CSAs) of segments corresponding to the nasal valve (CSA1), anterior portion (CSA2), and posterior portion (CSA3) of the lower turbinate, and the volumes at the nasal valve (V1) and turbinate (V2) regions at cleft and noncleft sides, before and after nasal decongestion with a topical vasoconstrictor. Nasometry was used to evaluate speech nasalance during the reading of a set of sentences containing nasal sounds and other devoid of nasal sounds. At the cleft side, before nasal decongestion, there was a significant increase (P < 0.05) in mean CSA1 and V1 values at POST1 and POST2 compared with PRE. After decongestion, increased values were also observed for CSA2 and V2 at POST2. No significant changes were observed at the noncleft side. Mean nasalance values at PRE, POST1, an POST2 were not different from each other in both oral and nasal sentences. The measurement of CSAs and volumes by acoustic rhinometry revealed that rhinoseptoplasty provided, in most cases analyzed, a significant increase in nasal patency, without concomitant changes in speech resonance, as estimated by nasalance assessment.

UBE2A Deficiency Syndrome: Mild to Severe Intellectual Disability Accompanied by Seizures, Absent Speech, Urogenital, and Skin Anomalies in Male Patients

We describe three patients with a comparable deletion encompassing SLC25A43, SLC25A5, CXorf56, UBE2A, NKRF, and two non-coding RNA genes, U1 and LOC100303728. Moderate to severe intellectual disability (ID), psychomotor retardation, severely impaired/absent speech, seizures, and urogenital anomalies were present in all three patients. Facial dysmorphisms include ocular hypertelorism, synophrys, and a depressed nasal bridge. These clinical features overlap with those described in two patients from a family with a similar deletion at Xq24 that also includes UBE2A, and in several patients of Brazilian and Polish families with point mutations in UBE2A. Notably, all five patients with an Xq24 deletion have ventricular septal defects that are not present inpatients with a point mutation, which might be attributed to the deletion of SLC25A5. Taken together, the UBE2A deficiency syndrome in male patients with a mutation in or a deletion of UBE2A is characterized by ID, absent speech, seizures, urogenital anomalies, frequently including a small penis, and skin abnormalities, which include generalized hirsutism, low posterior hairline, myxedematous appearance, widely spaced nipples, and hair whorls. Facial dysmorphisms include a wide face, a depressed nasal bridge, a large mouth with downturned corners, thin vermilion, and a short, broad neck. (C) 2010 Wiley-Liss, Inc.

Enhancement of the citrulline-nitric oxide cycle in astroglioma cells by the proline-rich peptide-10c from Bothrops jararaca venom

The biological activity of the proline rich decapeptde Bj PRO 10c a processing product of the C type natriuretic peptide precursor protein, expressed in the brain and the venom gland of the pit viper Bothrops jararaca, was originally attributed to the inhibition of the somatic angiotensm converting enzyme activity with subsequent ant hypertensive effect However recent results suggest broader biological activity may also be involved in the cardiovascular effects of this peptide Here we show that Bj PRO 10c enhances and sustains the generation of nitric made (NO) by regulating argininosuccinate synthase activity and thereby velocity of the citrulline NO cycle Bj PRO 10c-mediated effects not restricted to the cardiovascular system since NO production was also induced in cells of astroglial origin Bj PRO 10c was internalized by C6 astroglioma cells where it induces NO production and upregulation of the citrulline NO cycle cells in a dose dependent fashion In view of that, astroglial cells function as L arginine pool for NO production in neighboring neurons, we suggest a regulatory function for Bj PRO-10c on the metabolism of this gaseous neurotransmitter in the CNS Moreover, proliferation of astroglial cells was reduced in the presence of Bj PRO 10c however, cell death was not induced Since NO donors have been studied for the treatment of solid cancers Bj PRO 10c may serve as structural model for developing drugs to improve the effects of cancer therapy based on the peptide`s ability to augment NO production (C) 2010 Elsevier B V All rights reserved

Differential kinase requirement for enhancement of Fc gamma R-mediated phagocytosis in alveolar macrophages by leukotriene B(4) vs. D(4)

In alveolar macrophages, leukotriene (IT) B(4) and cysteinyl LTs (LTC(4), LTD(4) and LTE(4)) both enhance Fc gamma receptor (Fc gamma R)-mediated phagocytosis. In the present study we investigated the role of specific PKC isoforms (PKC-alpha and -delta), the MAP kinases p38 and ERK 1/2, and PI3K in mediating the potentiation of Fc gamma R-mediated phagocytosis induced by addition of leukotrienes to the AMs. It was found that exogenously added LTB(4) and LTD(4) both enhanced PKC-delta and -alpha phosphorylation during Fc gamma R engagement. Studies with isoform-selective inhibitors indicated that exogenous LTB(4) effects were dependent on both PKC-alpha and -delta, while LTD(4) effects were exclusively due to PKC-delta activation. Although both exogenous LTB(4) and LTD(4) enhanced p38 and ERK 1/2 activation, LTB(4) required only ERK 1/2, while LTD(4) required only p38 activation. Activation by both LTs was dependent on PI3K activation. Effects of endogenous LTs on kinase activation were also investigated using selective LT receptor antagonists. Endogenous LTB(4) contributed to Fc gamma R-mediated activation of PKC-alpha, ERK 1/2 and PI3K, while endogenous cysLTs contributes to activation of PKC-delta, p38 and PI3K. Taken together, our data show that the capacities of LTB(4) and LTD(4) to enhance Fc gamma R-mediated phagocytosis reflect their differential activation of specific kinase programs. (C) 2008 Elsevier Ltd. All rights reserved.

Enhancement of Th1 Lung Immunity Induced by Recombinant Mycobacterium bovis Bacillus Calmette-Guerin Attenuates Airway Allergic Disease

Mycobacterium bovis Bacillus Calmette-Guerin (BCG) has been shown to down-regulate experimental allergic asthma, a finding that reinforced the hygiene hypothesis. We have previously found that recombinant BCG (rBCG) strain that express the genetically detoxified Si subunit of pertussis toxin (rBCG-S1PT) exerts an adjuvant effect that enhances Th1 responses against BCG proteins. Here we investigated the effect of this rBCG-S1PT on the classical ovalbumin-induced mouse model of allergic lung disease. We found that rBCG-S1PT was more effective than wild-type BCG in preventing Th2-mediated allergic immune responses. The inhibition of allergic lung disease was not associated with increased concentration of suppressive cytokines or with an increased number of pulmonary regulatory T cells but was positively correlated with the increase in IFN-gamma-producing T cells and T-bet expression in the lung. In addition, an IL-12-dependent mechanism appeared to be important to the inhibition of lung allergic disease. The inhibition of allergic inflammation was found to be restricted to the lung because when allergen challenge was given by the intraperitoneal route, rBCG-S1PT administration failed to inhibit peritoneal allergic inflammation and type 2 cytokine production. Our work offers a nonclassical interpretation for the hygiene hypothesis indicating that attenuation of lung allergy by rBCG could be due to the enhancement of local lung Th1 immunity induced by rBCG-S1PT. Moreover, it highlights the possible use of rBCG strains as multipurpose immunomodulators by inducing specific immunity against microbial products while protecting against allergic asthma.

Enhancement on the Europium emission band of Europium chlortetracycline complex in the presence of LDL

Low-density lipoprotein (LDL) particles are the major cholesterol-carrying lipoprotein in the human circulation from the liver to peripheral tissues. High levels of LDL-Cholesterol (LDL-C) are known risk factor for the development of coronary artery disease (CAD). The most common approach to determine the LDLC in the clinical laboratory involves the Friedewald formula. However, in certain situations, this approach is inadequate. In this paper we report on the enhancement on the Europium emission band of Europium chlortetracycline complex (CTEu) in the presence of LDL. The emission intensity at 615 nm of the CTEu increases with increasing amounts of LDL. This phenomenon allowed us to propose a method to determine the LDL concentration in a sample composed by an aqueous solution of LDL. With this result we obtained LDL calibration curve, LOD (limit of detection) of 0.49 mg/mL and SD (standard deviation) of 0.003. We observed that CTEu complex provides a wider dynamic concentration-range for LDL determination than that from Eu-tetracycline previously. The averaged emission lifetimes of the CTEu and CTEu with LDL (1.5 mg/mL) complexes were measured as 15 and 46 Its, respectively. Study with some metallic interferents is presented. (C) 2010 Elsevier Inc. All rights reserved.

FUSION ENHANCEMENT/SUPPRESSION AND IRREVERSIBILITY IN REACTIONS INDUCED BY WEAKLY BOUND NUCLEI

We show that halo effects enhance fusion cross sections of weakly bound systems, comparing with the situation when there is no-halo. We introduce dimensionless fusion functions and energy variable quantity to investigate systematical trends in the fusion cross sections of weakly bound nuclei at near-barrier energies. We observe very clearly complete fusion suppression at energies above the barrier due to dynamic effects of the breakup on fusion. We explain this suppression in terms of the repulsive polarization potential produced by the breakup.

Understanding fusion suppression and enhancement in the (18)O+(58,60,64)Ni systems

Realistic coupled-channel calculation results for the (18)[O] + (58,60,64)Ni systems in the bombarding energy range 34.5 <= E(Lab) <= 6-5 MeV are presented. The overall agreement with existing experimental data is quite good. Our calculations predict an unexpected fusion suppression for above-barrier energies, with an important contribution of the two neutron ((18)O, (16)O) transfer channel couplings. The sub-barrier fusion enhancement and the above barrier suppression, predicted by the calculations, are consistent with the nuclear structure of the Ni region. Comparisons with recently reported similar effects in reactions induced by the (6)He projectile are discussed. (C) 2009 Elsevier B.V. All rights reserved.

Luminescence enhancement of the Tb(III) ion with the thenoyltrifluoroacetonate ligand acting as an efficient sensitizer

The synthesis, structural investigation, and photophysical properties of the complex [Tb(TTA)(2)(NO(3)) (TPPO)(2)] are reported. Unlike the analog tris-diketonate complex [Tb(TTA)(3)(TPPO)(2)], the new complex presents abnormally high luminescence intensity centered on the terbium ion. Our results clearly suggest a higher energy transfer efficiency from the TEA antenna ligand to the Tb(III) ion in the bis-diketonate complex compared with that in the tris-diketonate complex. A mechanism involving the increasing of triplet state energy when one TTA ligand is replaced by the NO(3)(-) group in the first coordination sphere is suggested and experimentally investigated to explain the anomalous luminescence properties of the new complex [Tb(TTA)(2)(NO(3))(TPPO)(2)]. (C) 2010 Elsevier B.V. All rights reserved.