Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5 Άγιος Νικόλαος
Κρήτη 72100
00302841026182
00306932607174
alsfakia@gmail.com

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Σάββατο 10 Φεβρουαρίου 2018

Repeatability of nasal allergen challenge results – further validation of the allergic rhinitis clinical investigator collaborative (AR-CIC) protocols

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Publication date: Available online 9 February 2018
Source:Annals of Allergy, Asthma & Immunology
Author(s): Mena Soliman, Lisa M. Steacy, Jenny Thiele, Dan E. Adams, Helen L. Neighbour, Anne K. Ellis
BackgroundNasal Allergen Challenge(NAC) models have been used to study allergic rhinitis and new therapies. Symptoms and biological samples can be evaluated at time points following allergen exposure.ObjectiveVerification of protocol repeatability and adequate interval between allergen exposures.Methods10 ragweed allergic participants were exposed to incrementally increasing dosages of ragweed allergen intra-nasally until they achieved a Total Nasal Symptom Score(TNSS) of 8/12 and a Peak Nasal Inspiratory Flow(PNIF) >=50% reduction from baseline. 3 weeks later participants were challenged with a cumulative dose equal to the sum of all the allergen doses received at screening. TNSS and PNIF were recorded at regular intervals including a 24h assessment. A repeat visit was conducted after a further 3 weeks. Nasal secretion samples were collected for cytokine and eosinophil quantification.Results9 participants completed all visits. TNSS and PNIF responses followed previous patterns, with an initial peak at 30 minutes followed by a gradual decline. Most participants reported similar patterns at both NAC visits, though some did not demonstrate the same phenotype at both visits. Some experienced a secondary symptom rise 24 hours following NAC. Eosinophil and cytokine sections followed a similar pattern at both NAC visits.ConclusionNAC is an adequate method for modelling AR in humans, demonstrating appropriate repeatability of symptoms, nasal mucosal eosinophil and cytokines. The 24h time point, previously not studied in our model, may be beneficial in evaluation of long acting medications. This 3 week interval NAC model will be beneficial for studies where before and after treatment comparisons are desired.



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Rapid oral desensitization protocol to abiraterone acetate

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Publication date: Available online 9 February 2018
Source:Annals of Allergy, Asthma & Immunology
Author(s): Miriam Verdu, Virginia Torres-Degayon, Mohamed Hassan-Bennis




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Learnings from a pragmatic pilot trial of text messaging for high risk adolescents with asthma

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Publication date: Available online 9 February 2018
Source:Annals of Allergy, Asthma & Immunology
Author(s): Cassandra M. Dodds, Maria T. Britto




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Age-related prevalence of chronic rhinosinusitis and nasal polyps and their relationships with asthma onset

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Publication date: Available online 9 February 2018
Source:Annals of Allergy, Asthma & Immunology
Author(s): Ha-Kyeong Won, Young-Chan Kim, Min-Gyu Kang, Han-Ki Park, Seung-Eun Lee, Min-Hye Kim, Min-Suk Yang, Yoon-Seok Chang, Sang-Heon Cho, Woo-Jung Song
BackgroundChronic rhinosinusitis (CRS) is a major disease condition with high morbidity, and may influence lower airway disease status in adults. However, its associations with adult asthma onset and activity have not been examined in detail in a general adult population.ObjectiveTo investigate the relationships between CRS with nasal polyps and asthma characteristics.MethodsA cross-sectional dataset from 17,506 adult participants (age≥18 years) in the Korean National Health and Nutrition Examination Survey 2010-2012 was analyzed. CRS was defined using structured questionnaires according to the international guideline, and presence of nasal polyps was objectively assessed using nasal endoscope. Presence of asthma and its onset and current activity were asked using structured questionnaires.ResultsCRS was significantly related with asthma, but the relationships were distinct by CRS and asthma status. CRS with nasal polyps (CRSwNP) was significantly associated with adult-onset asthma (onset after 18 years) or late-onset asthma (onset after 40 years), whereas CRS without nasal polyps (CRSsNP) were related to childhood-onset asthma (onset before 18 years) or early-onset asthma (onset before 40 years) in adults. Both CRS subgroups showed significant associations with current asthma but not with past asthma. However, comorbid asthma rate was less than 10% among subjects with CRS.ConclusionThis study found distinct age-related patterns of CRSwNP and asthma and demonstrated their significant associations in a general population. However, low prevalence of asthma in CRSwNP is in sharp contrast to the findings in Western populations, which warrants further investigation for ethnic or regional difference in CRSwNP-asthma relationships.



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Lack of effect of Grastek® on birch pollen-induced allergic rhinoconjunctivitis in the Environmental Exposure Unit

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Publication date: Available online 9 February 2018
Source:Annals of Allergy, Asthma & Immunology
Author(s): Anne K. Ellis, Mark W. Tenn, Lisa M. Steacy, Daniel E. Adams, Andrew G. Day, Terry J. Walker, Hendrik Nolte
BackgroundGrastek® is a standardized sublingual immunotherapy tablet(SLIT-T) approved for the treatment of grass pollen-induced allergic rhinitis(AR) and conjunctivitis. Many grass-allergic patients are also co-sensitized to birch pollen. Whether Grastek® can confer symptomatic benefits for birch pollen-induced AR symptoms is unknown.ObjectiveTo evaluate the treatment effect of Grastek® for birch pollen-induced AR in participants sensitized to both grass and birch pollen using the Environmental Exposure Unit(EEU).MethodsPhase IV, randomized, double-blind, placebo-controlled, parallel-group study enrolling participants aged 18-65 years allergic to both timothy grass and birch pollen. Following a baseline EEU birch pollen challenge where a minimum Total Nasal Symptom Score(TNSS) of 6/12 was required for enrollment, participants were randomized to receive Grastek® or placebo taken once daily for 4 months. No confirmatory grass pollen challenge was performed. The primary endpoint was the change in TNSS averaged from assessments from hours 2 to 5 during the post-treatment birch pollen challenge(PTC) compared to baseline. Secondary/exploratory endpoints included temporally identical changes in Total Ocular Symptom Score(TOSS), Total Rhinoconjunctivitis Symptom Score(TRSS), and individual symptom scores.ResultsThe difference in TNSS reduction following 4 months of therapy between the Grastek® and placebo group was not significant(P=0.83). Reductions in TOSS(P=0.19) and TRSS(P=0.67) were also comparable between groups. Findings between groups for individual symptom scores were similar(all P>0.4) except watery eyes where symptom reduction was slightly better in the placebo arm(P=0.014). Grastek® was well tolerated and no serious AEs occurred.ConclusionA by-stander effect of grass SLIT-T on birch pollen-induced AR symptoms was not detected. Symptomatic benefits of grass SLIT-T are likely allergen specific.



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Opioid and α2 adrenergic mechanisms are activated by GABA agonists in the lateral parabrachial nucleus to induce sodium intake

Publication date: Available online 9 February 2018
Source:Brain Research Bulletin
Author(s): Lisandra B. De Oliveira, Carina A.F. Andrade, Laurival A. De Luca, Débora S.A. Colombari, José V. Menani
The activation of GABA, opioid or α2 adrenergic mechanisms in the lateral parabrachial nucleus (LPBN) facilitates hypertonic NaCl intake in rats. In the present study, we combined opioid or α2 adrenergic antagonists with GABA agonists into the LPBN in order to investigate if NaCl intake caused by GABAergic activation in normohydrated rats depends on opioid or α2-adrenergic mechanisms in this area. Male Holtzman rats with stainless steel cannulas implanted bilaterally in the LPBN were used. Bilateral injections of muscimol or baclofen (GABAA and GABAB agonists, respectively, 0.5 nmol/0.2 μl) into the LPBN induced strong ingestion of 0.3 M NaCl (45.8 ± 7.3 and 21.8 ± 4.8 ml/240 min, respectively) and water intake (22.7 ± 3.4 and 6.6 ± 2.5 ml/240 min, respectively). Naloxone (opioid antagonist, 150 nmol/0.2 μl) into the LPBN abolished 0.3 M NaCl and water intake to muscimol (2.0 ± 0.6 and 0.9 ± 0.2 ml/240 min, respectively) or baclofen (2.3 ± 1.1 and 0.8 ± 0.4 ml/240 min, respectively). RX 821002 (α2 adrenoceptor antagonist, 10 nmol/0.2 μl) into the LPBN reduced 0.3 M NaCl intake induced by the injections of muscimol or baclofen (26.6 ± 8.0 and 10.1 ± 4.9 ml/240 min, respectively). RX 821002 reduced water intake induced by muscimol (7.7 ± 2.9 ml/240 min), not by baclofen. The results suggest that sodium intake caused by gabaergic activation in the LPBN in normohydrated rats is totally dependent on the activation of opioid mechanisms and partially dependent on the activation of α2 adrenergic mechanisms in the LPBN.



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Growth differentiation factor 11 improves neurobehavioral recovery and stimulates angiogenesis in rats subjected to cerebral ischemia/reperfusion

Publication date: Available online 9 February 2018
Source:Brain Research Bulletin
Author(s): Jingxi Ma, Lina Zhang, Tengfei Niu, Chibo Ai, Gongwei Jia, Xinhao Jin, Lan Wen, Keming Zhang, Qinbin Zhang, Changqing Li
The recent suggestion that growth differentiation factor 11 (GDF11) acts as a rejuvenation factor has remained controversial. However, in addition to its role in aging, the relationship between GDF11 and cerebral ischemia is still an important area that needs more investigation. Here we examined effects of GDF11 on angiogenesis and recovery of neurological function in a rat model of stroke.Exogenous recombinant GDF11 (rGDF11) at different doses were directly injected into the tail vein in rats subjected to cerebral ischemia/reperfusion (I/R). Neurobehavioral tests were performed, the proliferation of endothelial cells (ECs) and GDF11 downstream signal activin-like kinase 5 (ALK5) were assessed, and functional microvessels were measured.Results showed that rGDF11 at a dosage of 0.1 mg/kg/day could effectively activate cerebral angiogenesis in vivo. In addition, rGDF11 improved the modified neurological severity scores and the adhesive removal somatosensory test, promoted proliferation of ECs, induced ALK5 and increased vascular surface area and the number of vascular branch points in the peri-infarct cerebral cortex after cerebral I/R. These effects were suppressed by blocking ALK5.Our novel findings shed new light on the role of GDF11. Our results strongly suggest that GDF11 improves neurofunctional recovery from cerebral I/R injury and that this effect is mediated partly through its proangiogenic effect in the peri-infarct cerebral cortex, which is associated with ALK5. Thus, GDF11/ALK5 may represent new therapeutic targets for aiding recovery from stroke.



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