Triamcinolone Acetonide in the Treatment of Perennial Allergic Rhinitis: A post hoc Efficacy Analysis of a Phase III Study Performed in Russia.

INTRODUCTION: Allergic rhinitis (AR) is a disease which affects >24% of the population in Russia. Triamcinolone acetonide (TAA) is a corticosteroid used for treating AR. This post hoc analysis assesses the efficacy of intranasal TAA in improving perennial AR (PAR) symptom scores over 4 weeks. METHODS: NASANIF (NCT03317015) was a double-blind, parallel-group, multicenter, prospective, non-inferiority, phase III clinical trial in which patients with PAR were randomized (1:1) to receive TAA or fluticasone propionate (FP) over 4 weeks. Our post hoc analysis evaluates weekly change in PAR symptoms using the reflective Total Nasal Symptom Score (rTNSS), overall and for individual symptoms (sneezing, nasal itching, rhinorrhoea, and nasal obstruction). Proportion of patients and time to achieve a ≥50 or ≥75% reduction in rTNSS were assessed. For rTNSS endpoints, a linear mixed-model methodology was used; for time-to-event endpoints, cumulative incidence functions were estimated using the Kaplan-Meier method, in the per-protocol population. RESULTS: Of 260 patients, 128 each completed the study and were randomized to receive TAA or FP. From baseline to week 4, the changes in total rTNSS were -7.78 (95% CI: -8.1701 to -7.3967; p < 0.001) and -7.52 (-7.9053 to -7.1320; p < 0.001) for TAA and FP, respectively. Individual symptoms improved significantly from baseline. The proportion of patients achieving ≥50 and ≥75% reductions in total rTNSS was 88.0 and 67.2%, respectively in the TAA group. No significant differences were observed between the TAA and FP in any analyses. CONCLUSIONS: TAA produced effective and prolonged improvement of PAR symptoms over a 4-week treatment period.

Personalized medicine for allergy treatment: Allergen immunotherapy still a unique and unmatched model.

The introduction of personalized medicine (PM) has been a milestone in the history of medical therapy, because it has revolutionized the previous approach of treating the disease with that of treating the patient. It is known today that diseases can occur in different genetic variants, making specific treatments of proven efficacy necessary for a given endotype. Allergic diseases are particularly suitable for PM, because they meet the therapeutic success requirements, including a known molecular mechanism of the disease, a diagnostic tool for such disease, and a treatment blocking the mechanism. The stakes of PM in allergic patients are molecular diagnostics, to detect specific IgE to single-allergen molecules and to distinguish the causative molecules from those merely cross-reactive, pursuit of patient's treatable traits addressing genetic, phenotypic, and psychosocial features, and omics, such as proteomics, epi-genomics, metabolomics, and breathomics, to forecast patient's responsiveness to therapies, to detect biomarker and mediators, and to verify the disease control. This new approach has already improved the precision of allergy diagnosis and is likely to significantly increase, through the higher performance achieved with the personalized treatment, the effectiveness of allergen immunotherapy by enhancing its already known and unique characteristics of treatment that acts on the causes.

Toward personalization of asthma treatment according to trigger factors.

Asthma is a severe and chronic disabling disease affecting more than 300 million people worldwide. Although in the past few drugs for the treatment of asthma were available, new treatment options are currently emerging, which appear to be highly effective in certain subgroups of patients. Accordingly, there is a need for biomarkers that allow selection of patients for refined and personalized treatment strategies. Recently, serological chip tests based on microarrayed allergen molecules and peptides derived from the most common rhinovirus strains have been developed, which may discriminate 2 of the most common forms of asthma, that is, allergen- and virus-triggered asthma. In this perspective, we argue that classification of patients with asthma according to these common trigger factors may open new possibilities for personalized management of asthma.

Solar UV-B radiation and ethylene play a key role in modulating effective defenses against Anticarsia gemmatalis larvae in field-grown soybean.

Solar UV-B radiation has been reported to enhance plant defenses against herbivore insects in many species. However, the mechanism and traits involved in the UV-B mediated increment of plant resistance are unknown in crops species, such as soybean. Here, we studied defense-related responses in undamaged and Anticarsia gemmatalis larvae-damaged leaves of two soybean cultivars grown under attenuated or full solar UV-B radiation. We determined changes in jasmonates, ethylene (ET), salicylic acid, trypsin protease inhibitor activity, flavonoids, and mRNA expression of genes related with defenses. ET emission induced by Anticarsia gemmatalis damage was synergistically increased in plants grown under solar UV-B radiation and was positively correlated with malonyl genistin concentration, trypsin proteinase inhibitor activity and expression of IFS2, and the pathogenesis protein PR2, while was negatively correlated with leaf consumption. The precursor of ET, aminocyclopropane-carboxylic acid, applied exogenously to soybean was sufficient to strongly induce leaf isoflavonoids. Our results showed that in field-grown soybean isoflavonoids were regulated by both herbivory and solar UV-B inducible ET, whereas flavonols were regulated by solar UV-B radiation only and not by herbivory or ET. Our study suggests that, although ET can modulate UV-B-mediated priming of inducible plant defenses, some plant defenses, such as isoflavonoids, are regulated by ET alone.

The reduction of Cr(VI) in Salvinia minima, possible involvement of an h-type thioredoxin.

Hexavalent chromium [Cr(VI)] is extremely toxic to plant cells and has been recognized to possess a high redox potential. Tolerant plant species have shown the ability to reduce Cr(VI), but the operating mechanism involved in this process is not elucidated. Thus, the aim of this study was to investigate the possible involvement of thiolic and phenolic compounds and thioredoxin expression during Cr(VI) reduction in S. minima. In addition, a probable enzymatic reduction of Cr(VI) was investigated. Plants were exposed to 20 mg L-1 Cr(VI) concentration during 7 days under controlled conditions. The amount of metal accumulated in lacinias (root-like submerged leaves) and fronds (floating leaves) indicated that a low percentage of absorbed Cr(VI) was mobilized from lacinias to fronds. X-ray absorption near-edge structure (XANES) analysis revealed that Cr(III) was the only chromium species occurring in S. minima plants. Thiols and phenolics of lacinias and fronds were increased significantly by Cr(VI) treatment, but accumulation patterns were different. The expression of an h-type thioredoxin (Trx h) was demonstrated for the first time in Cr-exposed lacinias. Enzymatic reduction showed a low contribution to the Cr(VI) reduction. Data of this study provide evidences on the involvement of thiols, thioredoxin, and phenolics in the reduction of Cr(VI) to Cr(III) in S. minima tissues.

Case Report: Safe and Effective Sublingual Birch Allergen Immunotherapy in Two HIV-Positive Patients.

Allergen-specific immunotherapy (AIT) is a safe, effective treatment for respiratory allergies (such as moderate-to-severe allergic rhinoconjunctivitis) that are not controlled by symptomatic medications. The indications and contraindications for AIT have been defined in international guidelines and consensus statements. However, some of these contraindications are not evidenced- based but have been deduced from the theoretical risk of an interaction between AIT disease-modifying effect and immune or inflammatory comorbidities. In the absence of clinical trial evidence, the accumulation of experience as case reports can narrow the spectrum of absolute contraindications. The majority of international guidelines list HIV infection as a contraindication to AIT. Here, we describe two cases of safe, effective sublingual birch pollen AIT in HIV-positive patients undergoing concomitant antiretroviral therapy. A 32-year-old female and a 63-year-old male sensitized to tree pollen and with clinically confirmed birch pollen allergy underwent pre- and co-seasonal sublingual birch pollen AIT for three and two pollen seasons, respectively. The therapy was associated with a marked reduction in the frequency and intensity of allergic symptoms, and the reduced use of (symptomatic) rescue medication. Mild, local, treatment-emergent adverse events were noted throughout the course of treatment but resolved spontaneously. No serious adverse events were reported. In particular, there were no obvious harmful effects on the patients' immune status or viral load. Hence, sublingual birch pollen AIT proved to be effective and safe in two HIV-positive patients.

Proteases inhibitors-insensitive cysteine proteases allow Nezara viridula to feed on growing seeds of field-grown soybean.

The southern green stink bug, Nezara viridula is one of the primary soybean pests and causes significant economic losses around the world. In spite of the high proteases inhibitor (PI) levels, N. viridula can feed on developing seeds of field-grown soybean and reduce crop yields. Although the PI-induced responses have been extensively investigated in many pest insects, there is lack of knowledge about the mechanisms that stink bugs employ to withstand cysteine PIs of soybean seeds. This study demonstrated that feeding on developing seeds of field-grown soybean inhibited total proteases activity of N. viridula, as result of inhibition of cathepsin B-like activity in the gut. In addition, from the 30 digestive cathepsins recognized in this study, 6 were identified as cathepsin B-like. Stink bugs that fed on growing seeds of field-grown soybean had similar gut pH to those reared in the laboratory, and both cathepsin B- and L-like had an optima pH of 6.5. Therefore, using specific proteases inhibitors we found that the main proteolytic activity in the gut is from cysteine proteases when N. viridula feeds on soybean crops. Since cathepsin L-like activity was not inhibited by soybean PIs, our results suggested that N. viridula relays on cathepsin L-like to feed on soybean. To our knowledge no study before has shown the impact of seed PIs of field-grown soybean on digestive proteases (cathepsin B- and L-like) of N. viridula. This study suggests that the activity of PI-insensitive cathepsins L-like in the gut would be part of an adaptive strategy to feed on developing soybean seeds. In agreement, the expansions of cathepsin L-like complement observed in pentatomids could confer to the insects a higher versatility to counteract the effects of different PIs.

Glyphosate affects the larval development of honey bees depending on the susceptibility of colonies.

As the main agricultural insect pollinator, the honey bee (Apis mellifera) is exposed to a number of agrochemicals, including glyphosate (GLY), the most widely used herbicide. Actually, GLY has been detected in honey and bee pollen baskets. However, its impact on the honey bee brood is poorly explored. Therefore, we assessed the effects of GLY on larval development under chronic exposure during in vitro rearing. Even though this procedure does not account for social compensatory mechanisms such as brood care by adult workers, it allows us to control the herbicide dose, homogenize nutrition and minimize environmental stress. Our results show that brood fed with food containing GLY traces (1.25-5.0 mg per litre of food) had a higher proportion of larvae with delayed moulting and reduced weight. Our assessment also indicates a non-monotonic dose-response and variability in the effects among colonies. Differences in genetic diversity could explain the variation in susceptibility to GLY. Accordingly, the transcription of immune/detoxifying genes in the guts of larvae exposed to GLY was variably regulated among the colonies studied. Consequently, under laboratory conditions, the response of honey bees to GLY indicates that it is a stressor that affects larval development depending on individual and colony susceptibility.

A Japanese plum α-l-arabinofuranosidase/ß-D-xylosidase gene is developmentally regulated by alternative splicing.

A full-length cDNA clone named PsARF/XYL was obtained from Prunus salicina Lindl., and determined to encode a putative α-l-arabinofuranosidase/ß-d-xylosidase belonging to glycoside hydrolase (GH, EC 3.2.1.-) family 3. Two related PsARF/XYL cDNAs were amplified, one from a fully-spliced transcript (PsARF/XYLa) and another one from an intron-retained transcript (PsARF/XYLb). The protein deduced from PsARF/XYLb is a truncated peptide at C-terminus that conserves the active-site amino acid sequence. High levels of PsARF/XYLa and PsARF/XYLb transcripts are detectable in several plant tissues. PsARF/XYLb transcripts accumulate progressively during the phase of exponential fruit growth but they become barely noticeable during on-tree ripening, or after a 6-h exposure of preclimacteric full-size plums to ethylene. In contrast, PsARF/XYLa is expressed throughout fruit development, and transcript accumulation parallels the climacteric rise in ethylene production during ripening. PsARF/XYLa expression is strongly induced in preclimacteric full-size plums after a 6-h treatment with physiologically active concentrations of ethylene. These findings suggest that PsARF/XYL gene is post-transcriptionally regulated by alternative splicing during development and that ethylene may be involved in this regulation. The isolation of a partial cDNA clone, PsARF1, is also reported. It encodes a putative cell-wall α-l-arabinofuranosidase, and its transcription is rapidly inhibited by ethylene in mature green plums.