The serum levels of matrix metalloproteinase-9 (MMP-9) in neuropsychiatric disorders of adults have been widely investigated. So far, no studies have been conducted on the relationship of MMP-9 and cognitive domains in children with two phenotype models, attention deficit/hyperactivity disorder and hyperkinetic disorder (ADHD/HKD). The aim of this research was to evaluate and test the hypothesis that serum MMP-9 levels are associated with the severity of symptoms in children with ADHD/HKD and to compare the results in two models of this disorder. The study group comprised 37 Caucasian boys aged 7–12 years with HKD, being a subset of the combined ADHD subtype. Intellectual functions were measured using Wechsler Intelligence Scale for Children-Revised. The analysis of serum concentrations of MMP-9 was based on a quantitative sandwich ELISA. The statistical regression analysis revealed a correlation between increased serum MMP-9 levels and severity of symptoms in the ADHD (β = 0.33; p = 0.043) and HKD (β = 0.34, p = 0.037) model. According to the results, elevated levels of serum MMP-9 in boys with HKD may be associated with clinical impulsivity domain (β = 0.38; p = 0.019).
IntroductionInduced sputum is widely used in clinical practice and scientific studies. This technique has become enormously useful in assessment of airway inflammation. However, some asthmatics are unable to expectorate sputum of sufficient quality and quantity necessary for further processing, therefore not providing reliable results. This research study aimed to examine whether asthma control and asthma quality of life influence the results of sputum induction.Material and methodsFourty-seven adult subjects, current non-smokers with symptomatic asthma, were studied. All participants underwent clinical assessment, skin prick testing, spirometry and sputum induction. Before sputum induction, subjects were asked to fill in the Mini Asthma Quality of Life Questionnaire (MiniAQLQ) and Asthma Control Questionnaire (ACQ).ResultsTwenty-nine (62%) subjects produced sputum eligible for processing. This group had a significantly lower ACQ score (0.83 ±0.65 vs. 1.37 ±0.77; p = 0.02), higher MiniAQLQ total score (5.67 ±0.99 vs. 4.86 ±1.07; p = 0.011), higher MiniAQLQ symptoms domain score (5.54 ±1.13 vs. 4.63 ±1.24; p = 0.013) and higher MiniAQLQ activity limitations domain score (6.08 ±0.92 vs. 5.07 ±1.37; p= 0.014). The noted differences between groups of patients were not only statistically but were clinically important.ConclusionsThe study results suggest that successful sputum induction may be expected in patients with better asthma control and better quality of life.
Natural exposure may lead to an elevation of ENO in the patients with SAR without asthma. We estimate that the increased ENO may result from subclinical allergic inflammation present within the lower airways of nonasthmatic patients with SAR.
Combination of vincristine, doxorubicin and dexamethasone (VAD regimen) is a widely-used, effective and economic initial treatment of multiple myeloma (MM). However, between 30 and 50% of MM patients do not respond to VAD, and exposure to VAD may induce multi-drug resistance. Therefore, in the era of emerging novel therapies for MM, there is a need for pre-treatment identification of potential responders to VAD. Importantly, all three VAD components have common steps in their pathways of transport and metabolism, thus even modest inherited alteration caused by single nucleotide polymorphisms (SNP) may influence VAD efficacy an toxicity. The aim of this study was to investigate whether analysis of common functional SNP in drug transporter P-glycoprotein gene (MDR1 or ABCB1), phase I cytochrome P450A metabolizing enzymes genes (CYP3A4 and CYP3A5), phase II glutathione S-transferase P metabolizing enzyme gene (GSTP1) as well as in glucocorticoid receptor gene NR3C1 can be useful to predict response to VAD in MM. Fifty-two uniformly treated MM patients were investigated for 8 common SNPs including MDR1 exon 12 C1236T, MDR1 exon 21 G2677T/A, MDR1 exon 26 C3435T, CYP3A4*1B, CYP3A5*3, GSTP1 A313G as well as NR3C1 bcl I and NR3C1 N363S polymorphisms. Genotypes were identified using direct sequencing or RFLP methods. The response to VAD was estimated after administration of 3 courses of VAD, and patients who achieved complete or partial remission of MM were assigned as responders to VAD. In the cohort of included MM patients there were 39/52 (75%) responders to VAD. The analysis of the prognostic impact of the genotyped SNPs showed that carriers of P-glycoprotein gene MDR1 2677G allele had a significantly greater probability of achievement of the response to VAD as compared to the non-carriers, odds ratio(OR)=8.0, 95% confidence interval (95%CI)= 1.2–52.9, Fisher exact test p=0.031). Moreover, the predictive effect of MDR1 2677G allele was further increased by the presence of glucocorticoid receptor NR3C1 gene 363N allele. The carriers of both MDR1 2677G and NR3C1 363N alleles had 8.4-fold greater probability to achieve complete or partial remission with 3 courses of VAD (OR=8.40, 95% CI=1.8–40.0, p=0.008). Taken together, these data support the hypothesis that analysis of common functional polymorphisms in drug transporters, metabolizing enzymes and receptors may be useful for individualization of the initial therapy of MM. Particularly MDR1 G2677T/A and NR3C1 N363S SNPs can be considered as determinants of response to VAD therapy.
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