Group IIA phospholipase A2 content of tears in patients with atopic blepharoconjunctivitis

Background To determine the concentration of group IIA phospholipase A₂ (GIIAPLA₂) in tears of patients with atopic blepharoconjunctivitis (ABC), and to compare it with the GIIAPLA₂ concentration of tears in age-matched healthy controls.Methods The diagnosis of ABC was confirmed with a positive skin prick test and the presence of atopic dermatitis in lids. Conjunctival brush cytology was taken, and the cells including eosinophils, neutrophils, lymphocytes, squamous epithelial cells, columnar epithelial cells, metaplastic changes and the goblet cells were calculated separately. The GIIAPLA₂ concentration of tears was measured with a time-resolved fluoroimmunoassay in 29 patients with ABC (mean age 36.3±12.7 years) and 29 normal subjects (mean age 37.0±12.0 years).Results The GIIAPLA₂ concentration of tears in patients with ABC was 43.8±33.0 µg/ml, and in normal subjects it was 67.1±23.3 µg/ml. The difference was statistically significant (p=0.0018). The concentration of GIIAPLA₂ of tears was lowest in the subgroup of patients with ABC and dry eye (25.8 ±23.6 µg/ml), whereas it was only slightly decreased in patients with ABC and normal tear secretion (56.6±33.3 µg/ml). The difference between these two subgroups was statistically significant (p=0.011). There was no statistically significant correlation between the GIIAPLA₂ concentration of tears and the quantity of different conjunctival cells gathered by the brush cytology. However, an almost significant correlation was found between the GIIAPLA₂ concentration in tears and conjunctival eosinophils.Conclusions The results indicate that in patients with ABC the GIIAPLA₂ content of tears was decreased, without any dependence on the quantity of different conjunctival cells.     

Acute central nervous system toxicity during treatment of pediatric acute lymphoblastic leukemia: phenotypes,risk factors and genotypes

Central nervous system (CNS) toxicity is common at diagnosis and during treatment of pediatric acute lymphoblastic leukemia (ALL). We studied CNS toxicity in 1,464 children aged 1.0–17.9 years, diagnosed with ALL and treated according to the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol. Genome-wide association studies, and a candidate single-nucleotide polymorphism (SNP; n=19) study were performed in 1,166 patients. Findings were validated in an independent Australian cohort of children with ALL (n=797) in whom two phenotypes were evaluated: diverse CNS toxicities (n=103) and methotrexate-related CNS toxicity (n=48). In total, 135/1,464 (9.2%) patients experienced CNS toxicity for a cumulative incidence of 8.7% (95% confidence interval: 7.31–10.20) at 12 months from diagnosis. Patients aged ≥10 years had a higher risk of CNS toxicity than had younger patients (16.3% vs. 7.4%; P<0.001). The most common CNS toxicities were posterior reversible encephalopathy syndrome (n=52, 43 with seizures), sinus venous thrombosis (n=28, 9 with seizures), and isolated seizures (n=16). The most significant SNP identified by the genome-wide association studies did not reach genomic significance (lowest P-value: 1.11x10^-6), but several were annotated in genes regulating neuronal functions. In candidate SNP analysis, ATXN1 rs68082256, related to epilepsy, was associated with seizures in patients <10 years (P=0.01). ATXN1 rs68082256 was validated in the Australian cohort with diverse CNS toxicities (P=0.04). The role of ATXN1 as well as the novel SNP in neurotoxicity in pediatric ALL should be further explored.     

Tear fluid concentration of mmp–8 is elevated in non—allergic eosinophilic conjunctivitis and correlates with conjunctival inflammatory cell infiltration

Background  To investigate tear fluid concentration of matrix metalloproteinase 8 (MMP–8) and its relation to conjunctival inflammatory cell infiltration in persistent non—allergic eosinophilic conjunctivitis (NAEC). Methods  Two groups were included: 26 consecutive adult patients with NAEC (conjunctival eosinophils at least 1+ [1-10 eosinophils/slide], skin prick test [SPT] to common allergens negative), and 26 asymptomatic adult persons (no conjunctival eosinophils, SPT negative). MMP–8 tear fluid concentrations were determined by immunofluorometric assay, and conjunctival brush cytology samples from NAEC patients were used for MMP–8 immunocytochemistry. Gelatin zymography was used to illustrate proteolytic activity within the tear fluid samples. Results  The mean MMP–8 concentration was significantly higher among NAEC patients (214.3 ± 327.7 μg/l) than among healthy persons (50.4 ± 62.3 μg/l, P < 0.0001). In the NAEC patients, tear fluid MMP–8 correlated with the numbers of conjunctival neutrophils (r = 0.66, P = 0.0002) as well as with goblet cells and columnar epithelial cells (r = 0.54 for both, P = 0.045), but not with the lymphocyte numbers (r = -0.36, P = 0.0741). By immunocytology, MMP–8 protein could also be detected in vivo in the inflammatory cell population within the conjunctiva. Zymography revealed that proteolysis was significantly higher in the NAEC group, and activated enzymes were practically found only in the NAEC group. Conclusions  The results showed that NAEC is an inflammatory condition characterized by increased tear fluid MMP–8 levels, probably derived from both inflammatory and structural conjunctival cells. The increased proteolytic activity in NAEC patients may indicate risk of conjunctival structural changes (remodeling).     

Tear fluid levels of MMP-8 are elevated in ocular rosacea—treatment effect of oral doxycycline

Background  

Ocular rosacea (OcR) is a chronic inflammatory disease especially affecting lid margins. Previous studies have shown that it is accompanied by increased levels and activation of tear fluid gelatinases. Matrix metalloproteinase 8 (MMP-8; collagenase 2) levels and activation are commonly elevated in many inflammatory conditions. Therefore we studied here whether MMP-8 concentration and activation in tear fluid are increased also in OcR, and if an oral doxycycline regimen could rectify the situation.     

Allergic contact dermatitis is accompanied by severe abnormal changes in antioxidativity of blood.

We investigated whether the oxidative stress (OS) caused by skin inflammation could reflect in the blood, in a 21-year-old female student sensitized to nickel, colophony and abitole with often relapsing allergic contact dermatitis (ACD). As glutathione redox ratio was increased in the blood not only during the relapse but also in the beginning of remission phase, we prescribed natural medical preparations of d-alpha-tocopherol (in the first week 100 mg three times a day followed by 100 mg/day) and ascorbic acid (200 mg/day) for 25 days to her. After using antioxidants in the remission period, one of the principal OS markers-the glutathione redox ratio reached the normal physiological level. In this report, we showed that during acute extensive ACD OS is expressed in the blood and simultaneous supplementation of d-alpha-tocopherol and ascorbic acid might reduce systemic OS.     

Shaping Estonian primary school pupils’ values by using bullying-prevention methods

The purpose of this article is to identify to what extent using the methodology of the programme ‘Bullying-free school’, initiated in the Kingdom of Denmark in 2007 and implemented in schools in Estonia since 2013, has supported the development of ethical values in primary school pupils. The methodology focuses on four value attitudes: tolerance, respect, consideration and courage, and achieving these through developing a behavioural culture that attaches value to oneself, fellow-pupils and adults. The data were collected by means of a semi-structured focus group interview, addressing pupils’ behaviour, experience and feelings.

The study revealed that the bullying-prevention programme has developed joint values in school classes – tolerance, consideration, respect and courage, as well as an ability to think about these values and discuss them. Better results have been achieved in the classes where bullying prevention is conducted systematically and consistently.