Clinical characteristics and management of orbital apex syndrome: a 10-year multicentre experience.

BACKGROUND: Orbital apex syndrome (OAS) is a condition characterised by lesions within the orbital apex, leading to various ophthalmologic symptoms. This study aimed to analyse the clinical characteristics and treatment strategies of OAS with respect to aetiology. METHODS: This retrospective analysis utilised data from 5 medical institutions between 2013 and 2022. Patients who were diagnosed with OAS were initially enrolled, but patients who failed to follow up at least 1 month were excluded. The prevalence of initial ophthalmologic symptoms and visual improvement after treatment was compared according to aetiology. Factors related to visual improvement were analysed. RESULTS: Among 73 enrolled patients, the leading aetiology was tumours, followed by fungal infections and inflammation. Visual impairment and proptosis were prevalent in tumour-related OAS cases. Inflammation-related OAS exhibited a higher likelihood of painful eye movements and ophthalmoplegia. Ptosis was most frequently observed in fungal infection-related OAS. Notably, fungal infections emerged as the sole significant factor negatively impacting vision progression. In inflammation-related OAS, the time interval between symptom onset and the administration of steroids was longer in patients without visual improvement, even though there was no statistically significant difference. CONCLUSIONS: Tumours were the predominant cause of OAS. Visual impairment was a common manifestation in tumour-related OAS, while fungal infections were strongly associated with a poor visual prognosis. The timely administration of steroids might be helpful for improving vision in patients with inflammation-related OAS. However, further studies are needed to enhance understanding and management of OAS.

Lactococcus lactis KR-050L inhibit IL-6/STAT3 activation.

AIMS: The purpose of this study was to investigate IL-6/STAT3 inhibitory activity using lactic acid bacteria (LABs) isolated from Gajuknamu kimchi. METHODS AND RESULTS: Six LABs were isolated from Gajuknamu kimchi and identified through 16S rRNA sequencing. Among them, the culture broth of Lactococcus lactis KR-050L inhibited IL-6-induced STAT3 luciferase activity. Fifteen compounds were isolated from the EtOAc extract of culture broth though column chromatography and preparative high-performance liquid chromatography, and they were identified as 2,5-diketopipperazine structures by spectroscopic analyses (MS, 1 H- and 13 C-NMR). They also showed inhibitory activities on IL-6-induced STAT3 activation, and showed the different in activity according to the presence of a phenylalanine residue, hydroxyl groups and isometric structure. CONCLUSIONS: The six new LABs isolated from Gajuknamu kimchi, and Lc. lactis KR-050L was selected as candidate IL-6/STAT3 inhibitors. The activity levels of 15 2,5-DKPs isolated from Lc. lactis KR-050L were verified. SIGNIFICANCE AND IMPACT OF THE STUDY: This study constitutes the first attempt to isolate various LABs from Gajuknamu kimchi and to discover IL-6/STAT3 inhibitors in the EtOAc extract of Lc. lactis KR-050L culture broth. Moreover, our data provide useful biochemical information regarding the commercialization of Lc. lactis isolated from Gajuknamu kimchi as an approach to use functional foods for the treatment of various diseases via IL-6/STAT3 activation.

Navigation programs, are they helpful for perioperative care with thyroid cancer patients?

The purpose of this study was to develop and evaluate a navigation program for patients with thyroid cancer. The navigation program was developed following an analysis of the unmet needs of patients who underwent surgery for thyroid cancer. Ninety-nine patients in the control group received usual care, and 95 in the navigation group were managed with a navigation program during the perioperative period. The effectiveness of the navigation program was assessed by administering a questionnaire to both groups. Overall satisfaction scores were significantly higher in the navigation than in the control group (p = .025), as were satisfaction scores on the continuity of information (p < .001), the continuity of management (p = .002), the continuity of relationships with healthcare providers (p<.001), and patient empowerment (p < .001). The newly developed navigation program for patients with thyroid cancer was effective in raising satisfaction levels and in actively managing the disease during the perioperative period.

In vitro Solubility of Copper(II) Sulfate and Dicopper Chloride Trihydroxide for Pigs.

This study was conducted to determine the solubility of copper (Cu) in two sources of copper(II) sulfate (CuSO4) including monohydrate and pentahydrate and three sources of dicopper chloride trihydroxide (dCCTH) including α-form (dCCTH-α), ß-form (dCCTH-ß), and a mixture of α- and ß-form (dCCTH-αß) at different pH and a 3-step in vitro digestion assay for pigs. In Exp. 1, Cu sources were incubated in water-based buffers at pH 2.0, 3.0, 4.8, and 6.8 for 4 h using a shaking incubator at 39°C. The CuSO4 sources were completely dissolved within 15 min except at pH 6.8. The solubility of Cu in dCCTH-α was greater (p<0.05) than dCCTH-ß but was not different from dCCTH-αß during 3-h incubation at pH 2.0 and during 2-h incubation at pH 3.0. At pH 4.8, there were no significant differences in solubility of Cu in dCCTH sources. Copper in dCCTH sources were non-soluble at pH 6.8. In Exp. 2, the solubility of Cu was determined during the 3-step in vitro digestion assay for pigs. All sources of Cu were completely dissolved in step 1 which simulated digestion in the stomach. In Exp. 3, the solubility of Cu in experimental diets including a control diet and diets containing 250 mg/kg of additional Cu from five Cu sources was determined during the in vitro digestion assay. The solubility of Cu in diets containing additional Cu sources were greater (p<0.05) than the control diet in step 1. In conclusion, the solubility of Cu was influenced by pH of digesta but was not different among sources based on the in vitro digestion assay.

Development of a genetic marker set to diagnose aspirin-exacerbated respiratory disease in a genome-wide association study.

We developed a genetic marker set of single nucleotide polymorphisms (SNPs) by summing risk scores of 14 SNPs showing a significant association with aspirin-exacerbated respiratory disease (AERD) from our previous 660 W genome-wide association data. The summed scores were higher in the AERD than in the aspirin-tolerant asthma (ATA) group (P=8.58 × 10(-37)), and were correlated with the percent decrease in forced expiratory volume in 1 s after aspirin challenge (r(2)=0.150, P=5.84 × 10(-30)). The area under the curve of the scores for AERD in the receiver operating characteristic curve was 0.821. The best cutoff value of the summed risk scores was 1.01328 (P=1.38 × 10(-32)). The sensitivity and specificity of the best scores were 64.7% and 85.0%, respectively, with 42.1% positive and 93.4% negative predictive values. The summed risk score may be used as a genetic marker with good discriminative power for distinguishing AERD from ATA.

Immune response against 2,4-dinitrofluorobenzene-induced atopic dermatitis-like clinical manifestation is suppressed by spermidine in NC/Nga mice.

Of the biogenic polyamines, spermidine is a natural constituent of living cells and organisms. Spermidine is associated with regulation of cell growth, proliferation and differentiation, and with the suppression of oxidation and inflammation. Atopic dermatitis (AD) is a chronic inflammatory skin disease that has a complex and multiple pathogenesis, which includes genetic abnormality, modified or abnormal immune response and the production of nitric oxide and reactive oxygen species. We investigated whether spermidine can relieve AD-like clinical manifestation induced by the continual application of 2,4-dinitrofluorobenzene (DNFB) in NC/Nga mice. Spermidine at concentrations of 1 or 10 mg/kg reduced increasing ear swelling and attenuated oedema, haemorrhage and hyperkeratosis in AD-like skin lesions. Repetitive application of DNFB induced inflammatory cell infiltration to skin lesions, whereas intraperitoneal injection of spermidine inhibited DNFB-evoked infiltration of eosinophils, mast cells and T lymphocytes. Furthermore, spermidine suppressed mast cell degranulation and production of interferon-gamma by activated CD4(+) T cells in AD-like skin lesions. Spermidine may be a potential therapeutic agent for treatment of AD.

Secondary cutaneous lymphoma: comparative clinical features and survival outcome analysis of 106 cases according to lymphoma cell lineage.

BACKGROUND: The relative frequency, clinical features and survival outcomes of secondary cutaneous lymphoma remain poorly understood. OBJECTIVES: To determine the clinical characteristics and survival outcomes of secondary cutaneous lymphoma. MATERIALS AND METHODS: The present retrospective cohort study included all 106 patients who presented with secondary cutaneous lymphoma. Patient medical records were reviewed to determine the clinical features, survival outcomes and prognostic factors. Survival outcomes were analysed by using the Kaplan-Meier method and comparisons between lymphoma cell lineages [T or natural killer (T-/NK)-cell vs. B-cell lymphoma] were performed using the log-rank test. RESULTS: Secondary cutaneous lymphomas consisted of mature T-/NK-cell lymphomas (56%), mature B-cell lymphomas (35%), immature haematopoietic malignancies (8%) and Hodgkin lymphoma (1%). The T-/NK-cell lineage lymphoma cases were more likely to have multiple and disseminated skin lesions than the B-cell lineage lymphoma cases. The lymphoma cell lineage did not significantly influence survival outcomes. Patients who showed cutaneous involvement within 6 months of the initial diagnosis of primary disease had a poorer overall survival (OS) outcome than patients who developed cutaneous dissemination 6 or more months after the initial diagnosis (P < 0.001). Patients with disseminated skin lesions had a poorer OS than patients with localized skin lesions (P = 0.028). The two lymphoma cell lineages differed in terms of prognostic factors that influenced survival. CONCLUSIONS: Skin lesion characteristics such as time point of appearance and extent affect the survival outcomes of secondary cutaneous lymphoma. Cell lineage did not influence survival outcomes but the two lineages are associated with different prognostic factors.

Frequent visualization of thyroglossal duct remnant on post-ablation 131I-SPECT/CT and its clinical implications.

AIM: To evaluate the frequency of thyroglossal duct remnant (TGDR) uptake on post-therapy (131)I-scintigraphy in thyroid cancer patients, to analyse the rate of persistent TGDR uptake on follow-up combined (131)I-single-photon emission CT/CT (SPECT/CT), and to identify the differential clinical characteristics between patients with positive and negative TGDR uptake on (131)I-SPECT/CT. MATERIALS AND METHODS: A total of 179 patients treated with total thyroidectomy for thyroid cancer were enrolled in the study. At (131)I-whole-body scan (WBS), TGDR uptake was defined as an increase in radioactivity at the midline of the neck versus the thyroid bed. TGDR uptake on (131)I- SPECT/CT was defined as the presence of radioactivity at the expected pathway of the thyroglossal duct without evidence of metastatic foci. Persistent TGDR uptake was confirmed when TGDR uptake on follow-up (131)I-SPECT/CT corresponded to previous TGDR uptake detected by post-therapy (131)I-SPECT/CT. RESULTS: At SPECT/CT, TGDR uptake was noted in 86 of 179 patients. Stimulated thyroglobulin (sTg) levels were significantly higher (p = 0.02) in patients with positive TGDR uptake. Persistent TGDR uptake on follow-up (131)I-SPECT/CT was noted in 15 of 86 patients; sTg levels were significantly higher (p = 0.03) in the patients with persistent TGDR uptake. CONCLUSION: TGDR uptake is frequently visualized on post-therapy (131)I-SPECT/CT images and can be resistant to (131)I ablation. TGDR uptake has the potential to result in an elevation of serum thyroglobulin levels. (131)I-SPECT/CT clarifies TGDR uptake without additional invasive procedures or imaging studies, eliminating confusion among clinicians for managing differentiated thyroid cancer patients.

Effects of Feeding Barley Naturally Contaminated with Fusarium Mycotoxins on Growth Performance, Nutrient Digestibility, and Blood Chemistry of Gilts and Growth Recoveries by Feeding a Non-contaminated Diet.

The objectives of this study were to investigate the effects of feeding barley naturally contaminated with Fusarium mycotoxins on growth performance, vulva swelling, and digestibility of dry matter, organic matter, and crude protein of gilts and the recovery of gilts fed normal diets immediately after the exposure to contaminated diets by measuring growth performance and vulva swelling. In Exp. 1, four diets were prepared to contain 0%, 15%, 30%, or 45% contaminated barley containing 25.7 mg/kg deoxynivalenol and 26.0 µg/kg zearalenone. Sixteen gilts with an initial body weight (BW) of 33.3 kg (standard deviation = 3.0) were individually housed in a metabolism crate and assigned to 4 diets with 4 replicates in a randomized complete block design based on BW. During the 14-d feeding trial, individual BW and feed consumption were measured weekly and the vertical and horizontal lengths of vulva were measured every 3 d. From d 10, feces were collected by the maker-to-marker method for 4 d. Blood samples were collected on d 14. During the overall period, the average daily gain, average daily feed intake, and gain:feed of pigs linearly decreased (p<0.01) as the dietary concentration of contaminated barley increased. However, the digestibility of crude protein was linearly increased (p = 0.011) with the increasing amounts of contaminated barley. Increasing dietary Fusarium mycotoxin concentrations did not influence vulva size, blood characteristic as well as immunoglobulin level of pigs. In the Exp. 2, a corn-soybean meal-based diet was formulated as a recovery diet. Pigs were fed the recovery diet immediately after completion of the Exp. 1. During the 14-d of recovery period, the individual BW and feed consumption were measured weekly and the vertical and horizontal length of vulva were measured every 3 d from d 0. On d 7, the feed intake of pigs previously fed contaminated diets already reached that of pigs fed a diet with 0% contaminated barley and no significant difference in growth performance among treatments was observed during d 7 to 14 of the recovery period. In conclusion, increasing levels of mycotoxins in diets linearly decreased the growth performance of pigs, and these damages can be recovered in 7 d after the diet was replaced with a normal diet. The vulva size, blood characteristic, immune responses were not affected by increasing level of contaminated barley in the diets fed to pigs.

The highest prognostic impact of LDH among International Prognostic Indices (IPIs): an explorative study of five IPI factors among patients with DLBCL in the era of rituximab.

Although the International Prognostic Index (IPI) is considered as the current standard prognostication system for diffuse large B-cell lymphoma (DLBCL), prognostic heterogeneity is suggested to exist among the patients within the same IPI risk group. Hence, we investigated the pattern of distribution and prognostic impact of five IPI factors within the same IPI score. We retrospectively reviewed the medical records of 387 patients newly diagnosed as pathologically proven DLBCL between February 2002 and February 2010. We classified patients to IPI risk scores and categorized them according to the combinations of IPI. Then, we explored the frequency of five IPI factors and analyzed the correlation between these subgroups and efficacy outcomes: complete response (CR), event-free survival (EFS), and overall survival (OS). Survival estimates by IPI score in this cohort corresponded to the classic IPI. Elevated serum level of lactate dehydrogenase (LDH) was the most prevalently distributed factor throughout the scores, and patients with elevated serum level of LDH tended to have lower CR, inferior EFS, and/or OS irrespective of IPI scores. Particularly, among the subgroups of IPI score of 2, elevated serum level of LDH was significantly associated with inferior CR (73.1 vs 95.2 %), 3-year EFS (57 vs 87 %), and 3-year OS (58 vs 82 %). In addition, the higher serum level of LDH, particularly above 2,000 IU/L, was significantly correlated with the inferior survival outcomes (3-year EFS 78.0 vs 58.5 vs 45.5 vs 20.0 %, 3-year OS 86.0 vs 66.2 vs 58.2 vs 40.0 %). In conclusion, among five factors of IPI, elevated serum level of LDH seems to be the most frequently distributed and, more importantly, the most relevant IPI factor with the highest prognostic impact. These findings still warrant further validation in larger cohorts.

CT-based three-dimensional kinematic comparison of dart-throwing motion between wrists with malunited distal radius and contralateral normal wrists.

AIM: To compare motion of the capitate, scaphoid, and lunate in wrists with a malunited distal radius and contralateral normal wrists during dart-throwing motion (DTM) by three-dimensional kinematic studies using computed tomography (CT) images. MATERIALS AND METHODS: CT was performed simultaneously on both wrists in six patients with a unilateral distal radius malunion at three stepwise positions simulating DTM. Using volume registration technique, the kinematic variables of helical axis motion of the capitate, scaphoid, and lunate were calculated and compared between both wrists. The helical motion of the capitate was also evaluated in a scaphoid- and lunate-based coordinate system. RESULTS: Among the average rotation and translation of the scaphoid, lunate, and capitate during DTM, only the average rotation of the capitate was significantly different between the uninjured (88.9°) and the injured (70°) wrist (p = 0.0075). Rotation of the capitate relative to the scaphoid (26.3° versus 37.8°, p = 0.029) or lunate (39.2° versus 59.3°, p = 0.028) was smaller in the malunited wrist. The centres of helical axis motion of the three carpal bones were located more dorsally and radially in the injured wrist. CONCLUSIONS: The present study showed that decreased DTM in wrists with a distal radius malunion resulted from decreased midcarpal motion. The present study of the capitate, scaphoid, and lunate in wrists with distal radius malunion might be the first to present a 3D kinematic analysis of the effect of distal radius malunion on the carpal bones.

Differential lineage specification of thymic epithelial cells from bipotent precursors revealed by TSCOT promoter activities.

Mechanism of thymic compartmentalization was studied in the transgenic system using the promoter of thymic stromal cotransporter (TSCOT), a cortical thymic epithelium-specific gene. The transgenic 3.1 kb TSCOT (3.1T) and 4.4 kb TSCOT (4.4T) promoters recapitulated the thymic organ and the cortical epithelial cell-specific expression at the newborn stage. However, the 3.1T driving enhanced green fluorescent protein (EGFP; 3.1T-EGFP) or Cre-recombinase (3.1T-CreE) redistributed the expression into the medulla at the adult stages. Two Cre-transgenic lines (3.1T-CreE and 4.4T-CreE), when crossed with the ROSA LacZ or EGFP lines, showed the reporter expression in both the cortex and the medulla. TSCOT promoter activities were also verified in the transient thymic epithelial cell (TEC) population expressing keratin 5 and keratin 8. These indicate that the TSCOT promoter is turned on in the bipotent TEC precursors and regulated in a compartment-specific, developmentally regulated fashion. These transgenic lines provide the useful systems for delineating the specific pathways for TEC lineage development and function.

A multicenter, phase II trial of everolimus in locally advanced or metastatic thyroid cancer of all histologic subtypes.

BACKGROUND: This phase II study investigated the efficacy and safety of everolimus, an inhibitor of mammalian target of rapamycin (mTOR), in locally advanced or metastatic thyroid cancer. PATIENTS AND METHODS: Patients with thyroid cancer of any histology that was resistant or not appropriate for (131)I received everolimus 10 mg daily orally until unacceptable toxicity or disease progression. The primary end point was disease control rate [partial response (PR) + stable response ≥12 weeks]. Secondary end points included response rates, clinical benefit (PD + durable stable disease (SD)], progression-free survival (PFS), overall survival, duration of response, and safety. RESULTS: Thirty-eight of 40 enrolled patients were evaluable for efficacy. The disease control rate was 81% and two (5%) patients achieved objective response; their duration of response was 21+ and 24+ weeks. Stable disease (SD) and progressive disease was reported in 76% and 17% of patients, respectively. Seventeen (45%) patients showed durable SD (≥24 weeks) and clinical benefit was reported in 19 (50%) patients. Median PFS was 47 weeks [95% confidence interval (CI) 14.9-78.5]. Calcitonin, CEA, and thyroglobulin concentrations were ≥50% lower than baseline in three (30%) and four (44%) patients with medullary thyroid cancer and five (33%) patients with PTC, respectively. The most common treatment-related adverse events were mucositis (84%), anorexia (44%), and aspartate transaminase/alanine transaminase elevation (26%). CONCLUSIONS: Everolimus had a limited activity with low response rate in locally advanced or metastatic thyroid cancer. Reasonable clinical benefit rate and safety profile may warrant further investigation. CLINICALTRIALSGOV NUMBER: NCT01164176.

Apolipoprotein A1 potentiates lipoxin A4 synthesis and recovery of allergen-induced disrupted tight junctions in the airway epithelium.

BACKGROUND: Asthma is characterized by chronic airway inflammation triggered by various allergens in the environment. Defects in the bronchial epithelial interface with the external environment are the hallmark of asthma. Apolipoprotein A-1 (ApoA1) or ApoA1 mimetics have demonstrated anti-inflammatory activity and preventive effects in mouse models. OBJECTIVE: We investigated airway levels of ApoA1 in asthmatics and the possible role of ApoA1 in protection of the bronchial epithelium and in resolution of inflammation in cellular and animal models of asthma. METHODS: ApoA1 levels were measured in bronchoalveolar lavage fluid (BALF) from asthmatics and healthy controls. With treatment of ApoA1, mouse model of house dust mite (HDM)-driven asthma and cultured primary bronchial epithelial cells obtained from asthmatics were examined. Tight junction (TJ) expression in the bronchial epithelial cells was assessed by using confocal microscopy and immunoblot. RESULTS: Asthmatics showed significantly lower ApoA1 levels in bronchoalveolar lavage fluid than did healthy controls. Local ApoA1 treatment significantly decreased lung IL-25, IL-33, and thymic stromal lymphopoietin levels in HDM-challenged mice and inhibited allergen-induced production of these cytokines in cultured primary bronchial epithelial cells. ApoA1 promoted recovery of disrupted TJ proteins zonula occludens-1 and occludin in cultured primary bronchial epithelium obtained from asthmatics. ApoA1-induced increases in the TJ proteins were dependent on increased production of lipoxin A4 (LX A4). CONCLUSIONS AND CLINICAL RELEVANCE: ApoA1 enhances resolution of allergen-induced airway inflammation through promoting recovery of damaged TJs in the bronchial epithelium. ApoA1 could be a therapeutic strategy in chronic airway inflammatory diseases that are associated with a defective epithelial barrier, including asthma.

First measurement of the form factors in the decays D0 → ρ- e+ ν(e) and D+ → ρ0 e+ ν(e).

The beauty to up quark coupling constant |V(ub)| can be extracted from B → ρ e+ ν(e) combined with the form factors for D → K* e+ ν(e) and B → V ℓ+ ℓ- and D → ρ e+ ν(e). Using the entire CLEO-c ψ(3770) → DD event sample, corresponding to an integrated luminosity of 818 pb(-1) and approximately 5.4×10(6) DD events, we measure the form factors for the decays D0 → ρ- e+ ν(e) and D+ → ρ0 e+ ν(e) for the first time and the branching fractions with improved precision. A four-dimensional unbinned maximum likelihood fit determines the form factor ratios to be V(0)/A1(0)=1.48±0.15±0.05 and A2(0)/A1(0)=0.83±0.11±0.04. Assuming Cabibbo-Kobayashi-Maskawa unitarity, the known D meson lifetimes, and our measured branching fractions we obtain the form factor normalizations A1(0), A2(0), and V(0). We also present a measurement of the branching fraction for D+ → ω e+ ν(e) with improved precision.

Sustain and address discharge characteristics of AC-PDP with MgO surface coated by MgO nano crystal powders.

This paper examined the sustain and address discharge characteristics of ac-PDPs with MgO surface coated by MgO nano crystal powders. The MgO nano crystal powder was deposited by about 5% on the MgO surface by using the spray method. To investigate the effects of the partial addition of MgO nano crystal powders on the sustain discharge as well as the address discharge, the luminance, IR spectra of 823, 828 nm, cathodoluminance, and firing voltage were measured with the measurement of the address delay times and wall voltage variation in the 42-inch ac-PDP module with a high Xe content of 17%. As a result, the statistical delay characteristics were improved considerably especially under the low panel temperature of -5 degrees C for the MgO surface with MgO nano crystal powder. However, both MgO surfaces with and without the MgO nano crystal powder showed almost similar sustain and address discharge characteristics except the statistical delay characteristics.

Phylogenetic relationships of chrysanthemums in Korea based on novel SSR markers.

Chrysanthemums are well known for their esthetic and medicinal values. Characterization of chrysanthemums is vital for their conservation and management as well as for understanding their genetic relationships. We found 12 simple sequence repeat markers (SSRs) of 100 designed primers to be polymorphic. These novel SSR markers were used to evaluate 95 accessions of chrysanthemums (3 indigenous and 92 cultivated accessions). Two hundred alleles were identified, with an average of 16.7 alleles per locus. KNUCRY-77 gave the highest polymorphic information content value (0.879), while KNUCRY-10 gave the lowest (0.218). Similar patterns of grouping were observed with a distance-based dendrogram developed using PowerMarker and model-based clustering with Structure. Three clusters with some admixtures were identified by model-based clustering. These newly developed SSR markers will be useful for further studies of chrysanthemums, such as taxonomy and marker-assisted selection breeding.

Anti-IL-33 antibody has a therapeutic effect in a murine model of allergic rhinitis.

BACKGROUND: Interleukin (IL)-33 is involved in the Th2 immune response and could play an essential role in nasal allergy. Therefore, we aimed to investigate the therapeutic potential of anti-IL-33 for allergic rhinitis (AR). METHODS: Twenty-four BALB/c mice were used. In group A (control group, n = 6), mice were sensitized and challenged with saline. Group B [ovalbumin (OVA) group, n = 6] mice received intraperitoneal and intranasal OVA challenge. In group C (control IgG group, n = 6), mice were injected intraperitoneally with rabbit control IgG before OVA challenge. In group D (anti-IL-33 group, n = 6), anti-IL-33 was injected before challenge. We evaluated the number of nose-scratching events and external morphology; serum total and OVA-specific IgE; number of eosinophils, neutrophils, and lymphocytes in bronchoalveolar lavage (BAL) fluid; histopathologic examination of nasal cavity; and IL-4, IL-5, and IL-13 in BAL fluid. RESULTS: Anti-IL-33 treatment significantly reduced the nose-scratching events and ameliorated skin denudation. Serum total and OVA-specific IgE was significantly decreased in group D. The number of eosinophils in BAL fluid was also significantly decreased. Eosinophilic infiltration in the nasal cavity was significantly decreased in group D. IL-4, IL-5, and IL-13 in BAL fluid were also significantly decreased after treatment. CONCLUSIONS: Anti-IL-33 antibody has a therapeutic potential for experimental AR.

Ubiquitin-activating enzyme (UBA1) is required for sperm capacitation, acrosomal exocytosis and sperm-egg coat penetration during porcine fertilization.

Protein ubiquitination is a stable, covalent post-translational modification that alters protein activity and/or targets proteins for proteolysis by the 26S proteasome. The E1-type ubiquitin-activating enzyme (UBA1) is responsible for ubiquitin activation, the initial step of ubiquitin-protein ligation. Proteasomal proteolysis of ubiquitinated spermatozoa and oocyte proteins occurs during mammalian fertilization, particularly at the site of sperm acrosome contact with oocyte zona pellucida. However, it is not clear whether the substrates are solely proteins ubiquitinated during gametogenesis or if de novo ubiquitination also occurs during fertilization supported by ubiquitin-activating and -conjugating enzymes present in the sperm acrosome. Along this line of inquiry, UBA1 was detected in boar sperm-acrosomal extracts by Western blotting (WB). Immunofluorescence revealed accumulation of UBA1 in the nuclei of spermatogonia, spermatocytes and spermatids, and in the acrosomal caps of round and elongating spermatids. Thiol ester assays utilizing biotinylated ubiquitin and isolated sperm acrosomes confirmed the enzymatic activity of the resident UBA1. A specific UBA1 inhibitor, PYR-41, altered the remodelling of the outer acrosomal membrane (OAM) during sperm capacitation, monitored using flow cytometry of fluorescein isothiocyanate-conjugated peanut agglutinin (FITC-PNA). Although viable and motile, the spermatozoa capacitated in the presence of PYR-41, showed significantly reduced fertilization rates during in vitro fertilization (IVF; p < 0.05). Similarly, the fertilization rate was lowered by the addition of PYR-41 directly into fertilization medium during IVF. In WB, high Mr bands, suggestive of protein ubiquitination, were detected in non-capacitated spermatozoa by antibodies against ubiquitin; WB with anti-phosphotyrosine antibodies and antibodies against acrosomal proteins SPINK2 (acrosin inhibitor) and AQN1 (spermadhesin) revealed that the capacitation-induced modification of those proteins was altered by PYR-41. In summary, it appears that de novo protein ubiquitination involving UBA1 contributes to sperm capacitation and acrosomal function during fertilization.

Vasomotion does inhibit mass exchange between axisymmetric blood vessels and tissue.

Vasomotion, the name given to the physiological phenomenon whereby blood vessel walls exhibit rhythmic oscillations in diameter, is a complex process and very poorly understood. It has been proposed as a mechanism for protecting tissue when perfusion levels are reduced, since it has experimentally been shown to occur more frequently under such conditions. However, no quantitative evidence yet exists for whether the oscillation of the wall actually has any effect on mass transport to tissue. In our previous work, it was shown that the presence of non-linearities in the governing equation could result in a significant change in time-averaged mass transport to tissue: however, it was not possible, due to the limitations of the model, to determine whether time-averaged mass transport increased or decreased. This model is extended in this paper through coupling of the one-dimensional axisymmetric mass transport equations in tissue and blood to quantify the effects of vasomotion on mass transport to tissue. The results show that over a wide parameter range, surrounding those values calculated from experimental data, vasomotion does inhibit mass transport to tissue in a one-dimensional axisymmetric blood vessel by an amount that is predominantly dependent upon the amplitude of oscillation and that increases rapidly at larger oscillation amplitudes.