BackgroundQuilizumab, a humanized IgG1 monoclonal antibody, targets the M1-prime segment of membrane-expressed IgE, leading to depletion of IgE-switched and memory B cells. In patients with mild asthma, quilizumab reduced serum IgE and attenuated the early and late asthmatic reaction following whole lung allergen challenge. This study evaluated the efficacy and safety of quilizumab in adults with allergic asthma, inadequately controlled despite high-dose inhaled corticosteroids (ICS) and a second controller.MethodsFive hundred seventy-eight patients were randomized to monthly or quarterly dosing regimens of subcutaneous quilizumab or placebo for 36 weeks, with a 48-week safety follow-up. Quilizumab was evaluated for effects on the rate of asthma exacerbations, lung function, patient symptoms, serum IgE, and pharmacokinetics. Exploratory analyses were conducted on biomarker subgroups (periostin, blood eosinophils, serum IgE, and exhaled nitric oxide).ResultsQuilizumab was well tolerated and reduced serum total and allergen-specific IgE by 30–40 %, but had no impact on asthma exacerbations, lung function, or patient-reported symptom measures. At Week 36, the 300 mg monthly quilizumab group showed a 19.6 % reduction (p = 0.38) in the asthma exacerbation rate relative to placebo, but this was neither statistically nor clinically significant. Biomarker subgroups did not reveal meaningful efficacy benefits following quilizumab treatment.ConclusionsQuilizumab had an acceptable safety profile and reduced serum IgE. However, targeting the IgE pathway via depletion of IgE-switched and memory B cells was not sufficient for a clinically meaningful benefit for adults with allergic asthma uncontrolled by standard therapy.Trial registrationClinicalTrials.gov NCT01582503Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-016-0347-2) contains supplementary material, which is available to authorized users.

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Coetaneous malignant melanoma is the most aggressive cancer of the skin with a high rate of mortality worldwide. Degradation of basement membranes and extracellular matrix is an essential step in cancer invasion and metastasis. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play key roles in this step. MMP-3 also called stromelysin-1 was one of the first proteinases found to be associated with cancer. In the gene of MMP-3 (MMP3), an insertion/deletion of an A nucleotide at position -1171 in promoter region has been identified and shown to effect the expression activity of the gene.The present study was conducted to investigate the relation of MMP3 -1171insA polymorphism with skin malignant melanoma risk in a pilot case-control study of Bulgarian patients (n = 26) and unaffected controls (n = 172).The genotypes of controls and melanoma patients were in Hardy-Weinberg equilibrium. The results showed no statistically significant difference both in genotype and allele frequencies of MMP3 -1171insA polymorphism between melanoma patients and healthy controls either in crude analyses (p = 0.360 and 0.790, c2-test) or after adjustment for age and sex. The comparison of some clinical characteristics between the patients with different genotypes showed a trend for longer survival of patients with 6A/6A genotype compared to the carriers of 5A allele (5A/5A+5A/6A genotypes, p = 0.118, Log rank test).The results of our current preliminary study do not provide evidence for the role of the promoter polymorphism -1171insA in MMP3 as a risk factor for development of coetaneous melanoma, but suggest its implication in progression of the diseases.

Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow obstruction and is associated with chronic local and systemic inflammation and oxidative stress. The enhanced oxidative stress and inflammation have been reported to affect telomere length (TL). Furthermore, a number of SNPs at loci encoding the main components of the telomerase genes, TERT and TERC have been shown to correlate with TL. We aimed to explore the leukocyte TL and genotypes for single nucleotide polymorphisms, rs12696304 (C > G) and rs10936599 (C > T) near TERC in COPD cases and matched healthy controls using q-PCR technologies. Successful assessment of TL was performed for 91 patients and 88 controls. The patients had shorter TL (17919.36 ± 1203.01 bp) compared to controls (21 271.48 ± 1891.36 bp) although not significant (p = 0.137). The TL did not associate with the gender, age, spirometric indexes, smoking habits but tended to correlate negatively with BMI (Rho = − 0.215, p = 0.076) in the controls, but not in COPD patients. The genotype frequencies of the SNPs rs12696304 and rs10936599 were compared between patients and controls and the odds ratios (OR) for developing COPD were calculated. The carriers of the common homozygous (CC) genotypes of the SNPs had higher risk for COPD, compared to carriers of the variants alleles (rs12696304 CG+GG vs. CC; OR: 0.615, 95% CI [0.424–0.894], p = 0.011 and for rs10936599 CT+TT vs. CC OR = 0.668, 95% CI [0.457–0.976], p = 0.044). Analysis on the combined effects of the TERC rs12696304 (C > G) and rs10936599 (C > T) genotypes, CC/CC genotype combination was associated with higher risk for COPD (p < 0.0001) and marginally lower FEV1% pr. in patients with GOLD II (p = 0.052). There was no association between the SNP genotypes and TL. In summary, our results suggest that COPD patients may have shorter TL, and rs12696304 and rs10936599 near TERC may affect the risk of COPD independently of TL.

Abstract. The aim of the present study was to perform a zoo-hygienic assessment of lighting (natural and artificial) in different technological zones (stalls, manure and feed alleys) in semi-open freestall barns for dairy cows. The survey was conducted over a period of one year in 3 production buildings from 3 cattle farms located in three different areas of Southern Bulgaria - Stara Zagora District, Haskovo District and Plovdiv District. The building’s parameters were as follows: building No.1 - capacity 120 cows, 60.00/18.00/3.00m, 1080m2; building No.2 - capacity 120 cows, 66.00/18.00/3.00m, 1188m2 and building No.3 - capacity 500 cows, 90.00/45.00/3.30m, 4050m2. The premises lighting was measured with two combined apparatuses (Lutron EM-9300SD, 0-20000 lux and PU 150, 0-100000 lux), twice a month at 10.00, 12.00, 14.00, 16.00 and 18.00h at a height of 1m from the floor of the three technology zones. Summarized for all buildings, the light level varies widely by buildings, by seasons, by hours of reporting and by technological zones with limit values between 1 and 9810 lux. In all barns the most intense was the light above the feed alleys, followed by stalls and manure alleys; by hours of reporting during the day the level of lighting above the three technological zones was higher at midday (12.00-14.00h) compared to morning (10.00h) and afternoon (18.00h). Buildings No.1 and No.2 with a smaller built-up area provide more intensive lighting over all technological zones throughout all seasons compared to building No.3 with bigger built-up area: from 7.34 to 13.8 times over stalls, from 3.22 to 5.62 times over manure alleys and from 2.79 to 8.00 times over feed alleys. In buildings No.1 and No.2 there were prerequisites at least 16 hours of day light (photoperiod) to be provided during summer, autumn and spring, while in the winter months up to 8.00am and after 6.00pm the used artificial lighting was with low intensity and cannot provide the recommended over 160 lux intensity of the light. In building No.3 during most of the day for all seasons, the level of lighting above stalls and manure alley where the animals stay the longest time, the lighting level was lower than 160 lux. The factors ‘building’, ‘season’ and ‘hour of the day’ had a statistically significant effect (P<0.05-0.001) on the level of lighting in the three technological zones in the studied buildings. Of the associated factors, only the combination ‘season*hour of reporting’ had no significant effect on the lighting in the zones above the stalls and manure alleys.