Are atopy and eosinophilic bronchial inflammation associated with relapsing forms of chronic rhinosinusitis with nasal polyps?

Background

The aetiopathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) is still unknown. The role of atopy and the concept of united airways in such patients are still a matter of debate. In this pilot study we aimed at evaluating the degree of eosinophilic inflammation and the frequency of atopy in a cohort of CRSwNP patients candidate for Functional Endoscopic Sinus Surgery (FESS) and assessing the association between these factors and relapsing forms of CRSwNP.

Methods

30 patients (18 men, 12 women) with CRSwNP eligible for FESS were evaluated before and after surgery. Preoperative investigation included: history of previous relapse after FESS, clinical and laboratory allergologic assessment, spirometry, methacholine challenge, blood eosinophilia and determination of the fraction of nitric oxide in exhaled air (FeNO). Nasal fibroendoscopy, spirometry and FeNO determination were also assessed prospectively at 3 and 27 months post-FESS.

Results

18/30 subjects were atopic, 6/18 (33 %) were monosensitized, 16/30 (53 %) were asthmatics and 10/30 (33 %) had non steroidalantinflammatory drugs (NSAIDs) hypersensitivity. Twenty-one patients (70 %) were classified as relapsers, 15/18 (83 %) among atopics, 6/12 (50 %) among non atopics (p = 0.05). Among patients with NSAIDs hypersensitivity, 9/10 (90 %) were relapsers. The median IgE concentration was 161.5 UI/mL in relapsers and 79 UI/mL in non-relapsers (ns). The mean FeNO decreased after FESS (43.1–26.6 ppb) in 84 % of patients, but this effect disappeared over time (FeNO = 37.7 ppb at 27 months). Higher levels of FeNO pre-FESS were detected in atopics, and in particular in relapsing ones (median 51.1 ppb vs 22.1, ns). Higher levels of FeNO pre-FESS were detected in asthmatic patients, especially in those who relapsed (median: 67 vs 64.85 ppb in non-relapsed patients, ns). The Tiffeneau Index (FEV1/FVC) was significantly lower in asthmatic relapsers than in non relapsers asthmatics (94.7 ± 11.1 versus 105 ± 5.9—p = 0.04). Patients with asthma and atopy had a major risk of relapse (p = 0.05).

Conclusion

In our pilot study, atopy, severe asthma, bronchial inflammation, NSAIDs hypersensitivity and high level of total IgE are possible useful prognostic factors for the proneness to relapse after FESS. The role of allergy in CRSwNP pathogenesis should consequently be given deeper consideration. Allergen specific immunotherapy, combined with anti-IgE therapy, may have an immunomodulatory effect preventing polyps relapse and need to be investigated.

Electronic supplementary material

The online version of this article (doi:10.1186/s12948-015-0026-8) contains supplementary material, which is available to authorized users.     

Targeted mutation of the talpid3 gene in zebrafish reveals its conserved requirement for ciliogenesis and Hedgehog signalling across the vertebrates

Using zinc-finger nuclease-mediated mutagenesis, we have generated mutant alleles of the zebrafish orthologue of the chicken talpid3 (ta3) gene, which encodes a centrosomal protein that is essential for ciliogenesis. Animals homozygous for these mutant alleles complete embryogenesis normally, but manifest a cystic kidney phenotype during the early larval stages and die within a month of hatching. Elimination of maternally derived Ta3 activity by germline replacement resulted in embryonic lethality of ta3 homozygotes. The phenotype of such maternal and zygotic (MZta3) mutant zebrafish showed strong similarities to that of chick ta3 mutants: absence of primary and motile cilia as well as aberrant Hedgehog (Hh) signalling, the latter manifest by the expanded domains of engrailed and ptc1 expression in the somites, reduction of nkx2.2 expression in the neural tube, symmetric pectoral fins, cyclopic eyes and an ectopic lens. GFP-tagged Gli2a localised to the basal bodies in the absence of the primary cilia and western blot analysis showed that Gli2a protein is aberrantly processed in MZta3 embryos. Zygotic expression of ta3 largely rescued the effects of maternal depletion, but the motile cilia of Kupffer's vesicle remained aberrant, resulting in laterality defects. Our findings underline the importance of the primary cilium for Hh signaling in zebrafish and reveal the conservation of Ta3 function during vertebrate evolution.     

Oxidative stress and thyroid impairment after gibberellic acid treatment in pregnant and lactating rats and their offspring

Gibberellic acid (GA?) has been worldwide used in agriculture as a plant growth regulator. The purpose of this study is to assess the effects of GA? on the morphology and the thyroid hormone levels in adult rats and their suckling pups. Animals were given daily 200 ppm GA? in drinking water from the 14th day of pregnancy until day 14 after delivery. Compared with a control group, GA?-treated mothers and pups showed an increase in body and thyroid weights, a decrease in plasma FT? and FT? levels, which were more pronounced in pups than in their mothers. Thyroid iodine content was also decreased in pups. These biochemical modifications corresponded histologically; the majority of follicles had cubical epithelial cells, which surrounded empty vesicular cavities. Toxicity was objectified by a significant increase in plasma malondialdehyde, protein carbonyls, and advanced oxidation protein products levels in GA?-treated dams and their suckling pups; while, the activities of superoxide dismutase, catalase, and glutathione peroxidase were decreased in plasma of both dams and their pups. Moreover, a significant decline was observed in plasma glutathione, nonprotein thiols, and vitamin C levels. We conclude that GA? treatment affects thyroid function and plasma antioxidant status in adult rats and their progeny.     

Long-chain polyunsaturated fatty acids profile in plasma phospholipids of hyperphenylalaninemic children on unrestricted diet

IntroductionThe aim of the present study was to examine whether hyperphenylalaninemic children on unrestricted diet (MHP) may exhibit a different LCPUFA profile from PKU or healthy children in plasma phospholipids.Patients and methodsForty-five MHP children (age 9–14 years) were age and sex matched with 45 PKU and 45 healthy children. Fatty acids were determined and expressed as % of total fatty acids.ResultsMHP children showed docosahexaenoic acid (DHA) levels higher than PKU children (mean difference, 0.2%; 95% confidence interval, 0.02%–0.38%), although difference was not significant after correction for multiple comparisons, and lower levels than healthy children (?0.8%; ?1.01% to ?0.59%). Concentration of n-3 PUFA was higher in MHP than PKU children (0.6%; 0.4% to 0.8%),ConclusionsThe results suggest that low DHA levels in plasma phospholipids not only are evident in PKU but also may occur in MHP children, who are on unrestricted diet, as compared to healthy children.     

Métastase rénale d’un carcinome vésiculaire de la thyroïde révélée par le balayage du corps entier à l’iode 131

Distant metastasis of differentiated thyroid carcinoma generally affect lung and/or bone tissue. Renal metastasis from thyroid carcinoma is extremely rare. We report a case of renal metastasis from a follicular thyroid carcinoma in a 55-year-old man, occuring 11 years after total thyroidectomy, fortuitously discovered on a whole body scan carried out after 131-iodine therapy for neck recurrence of disease. Salient features of our clinical case are the fortuitous mode of discovery the unilateral localization of metastases and especially the long time interval which separates its detection from that of the primitive tumour. This case report exemplifies the useful role of the whole body scan carried out after 131-iodine therapy better adapted to reveal often undetectable occult metastases with low dose, but also to ensure a regular and protracted follow-up of patients treated for differentiated thyroid carcinoma.     

Tumeur du scalp : mode révélateur rare de carcinome vésiculaire thyroïdien

Cutaneous metastases of thyroid follicular carcinoma are rare. A scalp metastasis revealing a thyroid cancer is exceptional. We report the case of a 70 year-old women who presented with a scalp tumor progressively increased. Morphological imaging disclosed an important cutaneous tumor in occipital region with osteolysis. Surgical resection of this tumor was performed and pathology identified a cutaneous metastasis of a thyroid follicular cancer. This case report illustrates a rare presenting sign of thyroid follicular cancer. Cutaneous metastases coexists with other metastases (bone or lung) and means and ominous prognostic factor for the evolution of thyroid follicular cancer.     

A strategy to obtain axenic cultures of <Emphasis Type="Italic">Arthrospira</Emphasis> spp. cyanobacteria

A strategy to obtain axenic cultures of the cyanobacterium Arthrospira sp. (‘platensis’) Lefevre 1963/M-132-1 strain, consisting of a series of physical and chemical procedures, and the application of an optimized pool of antibiotics, is described in this paper. This strategy, which is an inexpensive and fast way to obtain axenic cultures, can be applied to Arthrospira spp. from culture collections or samples from their natural habitats to eliminate a wide spectrum of contaminants. A high alkaline treatment (pH 12, using KOH) of 72 h is a determinant initial procedure applied to eliminate protozoa and Microcystis sp. Bacteria were eliminated by an optimal antibiotic pool treatment, and Chroococcus sp. residuals were discarded by serial dilution. Optimal concentrations of the antibiotics composing the pool were obtained by a 2⁴ factorial central composite rotatable design (CCRD) and Response Surface Methodology (RSM), resulting in: ampicillin 61.6 μg/ml, penicillin 85.8 μg/ml, cefoxitin 76.9 μg/ml, and meropenem 38.9 μg/ml. The results also indicate that cefoxitin was the most effective antibiotic of this pool. After obtaining the axenic culture, identification of Lefevre 1963/M-132-1 strain was performed using amplification and sequencing of the ITS region (including part of 16S rRNA, tRNA Ile, ITS, tRNA Ala and part of 23S rRNA region) and fatty acid composition data. Data base comparison revealed that Lefevre strain is closely related to A. platensis species (99% identity), while fatty acid composition data suggested A. maxima. These seemingly contradictory results are discussed.     

Joining forces: feedback and integration in plant development

Feedback and integration of information are of paramount importance for the robust functioning and dynamics of biological systems. In plant developmental biology, experimentation is increasingly combined with computational modeling to obtain a better understanding of how such regulatory interactions shape the systems' behavior. Here we highlight experimental and modeling studies on feedback loops and integration mechanisms involved in plant development. These studies have substantially expanded our understanding of previously characterized gene regulatory networks (GRNs). In addition, they illustrate the pervasiveness of regulatory interactions between seemingly unrelated processes and levels of organization. Modelers in plant development will increasingly face the challenges of what level of detail, which processes and how many levels of organization to incorporate when trying to understand a particular process.     

Substitution at carbon 2 of 19-nor-1α,25-dihydroxyvitamin D3 with 3-hydroxypropyl group generates an analogue with enhanced chemotherapeutic potency in PC-3 prostate cancer cells

The active form of vitamin D(3), 1α,25-dihydroxyvitamin D(3)(1α,25(OH)(2)D(3)), has anti-proliferative and anti-invasive activities in prostate cancer cells. Because of 1α,25(OH)(2)D(3) therapeutic potential in treating cancers, numerous analogues have been synthesized with an attempt to increase anti-proliferative and/or decrease calcemic properties. Among these analogues, 19-nor-1α,25(OH)(2)D(2) while being less calcemic has equivalent potency as 1α,25(OH)(2)D(3) in several in vitro and in vivo systems. We recently showed that 19-nor-2α-(3-hydroxypropyl)-1α,25(OH)(2)D(3) (MART-10) was at least 500-fold and 10-fold more active than 1α,25(OH)(2)D(3) in inhibiting the proliferation of an immortalized normal prostate PZ-HPV-7 cells and the invasion of androgen insensitive PC-3 prostate cancer cells, respectively. In this study, we further investigated the effects of MART-10 and 1α,25(OH)(2)D(3) on the dose- and time-dependent induction of CYP24A1 gene expression in PC-3 prostate cancer cells. We found that MART-10 induced CYP24A1 gene expression at a lower concentration with a longer duration compared to 1α,25(OH)(2)D(3), suggesting that MART-10 is less susceptible to CYP24A1 degradation. Molecular docking model of human CYP24A1 and MART-10 indicates that its side chain is far away from the heme ion and is less likely to be hydroxylated by the enzyme. Furthermore, MART-10 was a more potent inhibitor of PC-3 cell proliferation and invasion compared to 1α,25(OH)(2)D(3). In addition, MART-10 down-regulated matrix metalloproteinase-9 (MMP-9) expression which could be one mechanism whereby MART-10 influences cancer cell invasion. Finally, we observed that subcutaneous administration of MART-10 up-regulated the CYP24A1 mRNA expression in rat kidneys without affecting their plasma calcium levels. Thus, our findings demonstrate that MART-10 is biologically active in vivo and may be an effective vitamin D analogue for clinical trials to treat prostate cancer.