Comparison of the impact of childhood psoriasis on mothers' and fathers' quality of life - does gender of a caregiver play a role?

BACKGROUND: Psoriasis is a chronic skin condition that in one third of cases starts in the first two decades of life. The disease might impact the quality of life (QoL) of the affected children and their caregivers. The issue of gender differences in the assessment of psychological burden of dermatological conditions has been the subject of few studies with contradictory results. OBJECTIVES: The aim of this study was to investigate the differences in the impact of childhood psoriasis on mothers' and fathers' well-being using Family Dermatology Life Quality Index (FDLQI). METHODS: Forty-five children with psoriasis (31 girls and 14 boys; mean age ± standard deviation (SD) 10.53 ± 3.44 years) and their parents (45 mothers and 45 fathers) were included in the study. Both parents of each child were asked to separately fill in the validated Polish version of the FDLQI questionnaire. RESULTS: Comparing the FDLQI scores, the QoL of mothers was significantly more impaired than the QoL of fathers (13.44 ± 6.46 versus 9.53 ± 6.12 points; P < 0.0001). In mothers, childhood psoriasis had a significantly greater impact in the areas of emotional distress (P = 0.007), dealing with other people's reactions (P < 0.0001), social life (P = 0.02), amount of time spent caring for the child's skin (P = 0.0001) and extra housework (P = 0.0005), compared to fathers. The FDLQI scores of both mothers and fathers were independent of the impairment of children's QoL or the severity of psoriasis, except for positive correlation between mothers' FDLQI scores and children's BSA (R = 0.31; P = 0.03). CONCLUSIONS: Differences in the impact of childhood skin diseases on mothers' and fathers' well-being should be taken into consideration while developing educational programmes for patients and their families. There is a need for further, multi-centre research that would take into account geographical and cultural differences, in order to reliably assess the impact of childhood psoriasis on various aspects of caregivers' QoL.

The 7-day mortality associated with an early warning score varies between age groups in a cohort of adult Danish emergency department patients.

INTRODUCTION: Early warning scores are designed for monitoring hospitalized patients and enable a timely response to deviating vital signs. The aim of this study was to examine whether 7-day mortality, associated with an initial early warning score, differs between age groups. Our hypothesis was that elderly patients are at greater risk of dying compared to a younger patient with a similar early warning score. METHODS: This observational cohort study included adult emergency department patients from five hospitals in Denmark over three consecutive months in 2015. Logistic regression was used to examine the relationship between patients' initial early warning scores category (0, 1-2, 3-4, 5-6, 7+) and 7-day mortality in different age groups (16-59 years, 60-79 years, 80+ years). Mortality rates in each early warning scores category are compared between the youngest patients (16-59 years, reference group) and the two older age groups (60-79 years and 80+ years). RESULTS: A total of 19 123 emergency patients were included. The senior age groups (60-79 years and 80+ years) both displayed significantly higher 7-day mortality, in all early warning score categories, when compared to the youngest patients (16-59 years). The mortality difference between the youngest (16-59 years) and oldest age group (80+ years) remained significant in all early warning scores categories after adjusting for comorbidity. CONCLUSION: Our findings show that the oldest emergency department patients (80+ years) have a higher 7-day mortality compared to young patients (16-59 years) with a similar initial early warning score.

The Influence of FTO Polymorphism rs9939609 on Obesity, Some Clinical Features, and Disturbance of Carbohydrate Metabolism in Patients with Psoriasis.

BACKGROUND: Psoriasis is often accompanied by obesity, hyperlipidemia, diabetes, and metabolic syndrome as risk factors of cardiovascular conditions and premature mortality. OBJECTIVE: The study was aimed at investigating whether psoriatic patients, who carry risk allele of obesity-related FTO gene, are more predisposed to obesity and metabolic disturbances and whether it influences the severity of psoriasis. METHODS: 197 patients with psoriasis, representing Lower Silesia region of Poland, underwent physical examination and anthropometric measurements. Blood samples for biochemical and genetic analysis were collected. All patients were genotyped for FTO gene rs9939609 variant. Identification of SNP was conducted with the use of minisequencing method. RESULTS: Around 63% of patients were carriers of at least one risk allele A and 20% were AA homozygotes. The A allele was associated with increased BMI and hip and waist circumferences. The carriers of risk allele had increased PASI and CRP values and tended to have an increased insulin concentration. CONCLUSION: Psoriatic patients, carriers of risk allele of FTO gene rs9939609, have an increased risk for more severe psoriasis and obesity and may develop obesity-induced insulin resistance.

Role of galectin-3 in subclinical myocardial impairment in psoriasis.

BACKGROUND: Psoriasis has been shown to increase cardiovascular risk, and a contributor to this might be enhanced myocardial fibrosis promoted by the disease-associated pro-inflammatory milieu. OBJECTIVE: We sought to investigate the relationship of galectin-3 (Gal-3) - a recognized mediator of fibrosis with inflammatory activation and left ventricular (LV) systolic and diastolic function in patients with psoriasis. METHODS: We enrolled 102 psoriatic patients (mean age: 52.5 ± 12.6 years). Sixty-five age- and sex-matched healthy subjects served as controls. Echocardiographic assessment of myocardial function included estimation of LV longitudinal systolic deformation (GLS) and diastolic indices: tissue e' velocity and E/e' ratio. Laboratory measurements encompassed blood Gal-3, creatinine, glucose, insulin, CRP and erythrocyte sedimentation rate (ESR). RESULTS: Patients with psoriasis were characterized by elevated Gal-3 (12.3 [9.3-13.4] vs. 6.3 [5.5-9.4] ng/mL in healthy controls, P < 0.001), ESR (17.0 [11.0-29.0] vs. 8.5 [6.0-13.0] mm, respectively, P < 0.001) and CRP (3.1 [1.7-10.6] vs. 1.9 [1.5-4.0] mg/L, respectively, P < 0.001), and reduced GLS (19.9 ± 3.7 vs. 22.0 ± 3.0%, respectively, P < 0.001). Progressive deterioration of GLS was demonstrated across Gal-3 tertiles. Significant associations between GLS and age (beta = -0.21, P < 0.04), Gal-3 (beta = -0.27, P < 0.01), CRP (beta = -0.22, P < 0.03), ESR (beta = -0.25, P < 0.01), waist circumference (beta = -0.22, P < 0.03) and waist-to-hip ratio (beta = -0.20, P < 0.05) were found. Stepwise multiple regression analysis revealed that the independent determinants of GLS in psoriatic patients were Gal-3 (beta = -0.24, P < 0.01) and ESR (beta = -0.21, P < 0.03). Regression-based mediation analysis demonstrated that the relationship between ESR and GLS was partially mediated by Gal-3. CONCLUSIONS: Subclinical left ventricular systolic dysfunction in psoriasis, as evidenced by reduced GLS, is linked with the inflammatory upregulation, and enhanced profibrotic activity (as reflected by elevated serum Gal-3) may be involved in this process. These putative mechanisms may be responsible for the observed higher incidence of heart failure in this disease condition and should be considered as a potential target for preventive and therapeutic measures.

Methotrexate in the treatment of mycosis fungoides - a multicenter observational study in 79 patients.

OBJECTIVE: The first report concerning methotrexate (MTX) in the treatment of Mycosis fungoides (MF) was published in 1964 by Wright. The mechanism of MTX action in the treatment of primary cutaneous T-cell lymphoma (CTCL) has been not explained in detail yet (the anti-inflammatory, immunomodulating, immunosuppressive, and cytostatic actions have been under discussion). PATIENTS AND METHODS: This is a retrospective analysis of 79 MF patients in 4 dermatology clinical centers in Poland. Data are presented in terms of the duration, use of MTX, the effectiveness of treatment with MTX in terms of time required to achieve remission, the disease stage, route of administration, age at diagnosis and the dosage. Moreover, the occurrence of side effects depending on the route of administration and duration of therapy with MTX was analyzed. RESULTS: The analysis has revealed that 56 patients (70,9%) had achieved remission on the MTX. The remission began in the 1st month of therapy in 20% of patients, lasted 4 to 6 months in 50% of cases. At least 12 months' remission was confirmed in 25% of patients (2-year-long only in 10% and 3-year-long in 5% of patients). The time to remission was related to the stage of disease at diagnosis as well as to minimal and maximal dose of MTX. The total therapeutic dose of MTX was found important for the course of the disease: higher total dose had prolonged the remission. CONCLUSIONS: Despite the common use of MTX in MF patients, relatively few clinical studies have been published. The response of MF subjects to MTX seems to depend on the stage and, more importantly, the dose of MTX treatment. Methotrexate appears to be an effective treatment at every stage of MF; however, it is not devoided of side effects such as infections and elevated level of aminotransferases, which are most common.

The new insight into the role of antimicrobial proteins-alarmins in the immunopathogenesis of psoriasis.

The pathognesis of psoriasis still remains not fully elucidated. Recent advances favor the idea that interactions between innate and adaptive immune response drive inflammatory process in this disease. Innate antimicrobial peptides and proteins (AMPs) are diverse group of small molecules that provide the first line of defense against invading pathogens. In recent years, the novel functions of AMPs have been identified. There are three subclasses among AMPs that have gained the special interest as a potentially important player in the pathogenesis of psoriasis: cathelicidin, S100 proteins, and defensins. These AMPs have been shown to modulate and trigger host immune response in psoriasis acting as interplayer between innate and adaptive immune mechanisms. Overexpressed in psoriatic lesions, they prime immune cells for enhanced production of proinflammatory mediators and act as chemoattractant for leukocytes. Therefore, the novel term describing AMPs alarmins has been suggested. As multifunctional player in pathogenesis of psoriasis, AMPs may constitute potential target for therapeutic interventions. However, further investigations are required to establish the methods of downregulation of the aberrant proinflammatory functions of AMPs without increasing the risk of infections.

Altered microRNA expression in mycosis fungoides.

BACKGROUND: MicroRNAs are small noncoding RNA molecules involved in the regulation of various physiological and pathological processes. Altered expression of different microRNAs has been observed in both solid tumours and haematological malignancies. OBJECTIVES: To investigate expression of several microRNAs in early and advanced mycosis fungoides (MF). METHODS: Biopsies were obtained from 43 patients with MF (18 early MF and 25 advanced MF) and 23 healthy volunteers. After microRNA isolation, reverse transcriptase reactions were performed, followed by cDNA amplification. The following microRNAs were analysed: miR-15a, miR-16, miR-155, let-7a, let-7d and let-7f. The relative amount of each microRNA was normalized according to the reference RNU48 level. RESULTS: Among the microRNAs studied, only MiR-155 was found to be slightly overexpressed in MF compared with healthy controls. Early MF showed a higher level of all analysed microRNAs after normalization against RNU48 level. Furthermore, metastatic MF demonstrated lower concentrations of let-7a, let-7d and let-7f when compared with MF limited to the skin. The univariate survival analysis and multivariate Cox's regression model revealed that the level of let-7a expression was an independent prognostic indicator. CONCLUSIONS: Altered expression of studied microRNAs and the differences between early and advanced MF may suggest that microRNAs play a significant role in MF pathogenesis. It seems that microRNAs could serve as potential therapeutic targets in the future.

Periungual lesions in pyoderma gangrenosum.

Pyoderma gangrenosum (PG) is a progressive cutaneous necrosis of unknown origin. We report a case of PG presenting with periungual lesions. A 57-year-old woman was on treatment with ciclosporin A for PG. During tapering of the ciclosporin A dose, proliferating periungual lesions developed on the third and fourth finger of the left hand, the fourth finger of the right hand, and on the right great toe and the left fifth toe. All lesions appeared within a 4-week period. These abnormalities were ulcerated, involved about one-third of the distal part of the lateral nail folds including the part of nail fold bordering on the free edge of the nails, and were very painful. The skin biopsy was consistent with that seen in PG. Increasing the ciclosporin A dose led to significant improvement in the periungual lesions within the next few weeks and complete resolution within 6 months.

Molecular analysis of the nucleoprotein gene of canine distemper virus isolated from clinical cases of the disease in foxes, minks and dogs.

In this study, we used RT-PCR to detect and characterize canine distemper virus isolated from 9 naturally infected foxes, 3 minks and 3 dogs in Poland by amplifying and sequencing a portion of the NP gene. A 293-bp fragment of the CDV NP gene was amplified by RT-PCR. Sequencing of the PCR products from the isolates led to the identification of 3 sequence variants. The mostly representative polymorphic variant No. 1 showed high homology with Chinese isolate of CDV with a accession number EF 375619. The sequences of all isolates from this polymorphic variants compared with the sequences of other polymorphic variants obtained in the study and with European and American isolates sequences from GenBank showed the conservative nucleotides changes in positions 57, 132, 143, 159 and 237. These mutations can indicate that in this part of Europe there are new variants of CDV.

The involvement of cerebellar dopamine D3 receptors in locomotor activity of rats.

A preferential agonist of dopamine D3 receptors, 7-hydroxy-N-N-di-n-propyl-2-aminotetralin (7-OH-DPAT), injected into the cerebellar lobules 9 and 10 (0.001-10 microg/0.5 microl) dose-dependently reduced locomotor activity of rats. 7-OH-DPAT injections into the lobule 8 were ineffective. The 7-OH-DPAT-induced hypolocomotion was inhibited by intracerebellar (0.9 microg/0.5 microl) or systemic (0.2 mg/kg sc) injection of a selective D3 receptor antagonist, (3aR,9bS)-N-[4-(8-cyano-1,3a,4,9b-tetrahydro-3H-benzopyrano[3,4-c]pyrrole-2-yl)-butyl]-(4-phenyl) benzamide (S33084). The present results indicate that dopamine D3 receptors in lobules 9 and 10 contribute to 7-OH-DPAT-induced hypolocomotion.

GC-MS Analysis of beta-Carotene Ethenolysis Products and their Synthesis as Potentially Active Vitamin A Analogues.

beta-Carotene ethenolysis under promotion of well-defined ruthenium catalysts were examined as a novel method of synthesis of vitamin A derivatives. Efficient reaction was promoted by the second-generation Hoveyda catalyst. The products of ethenolysis in positions C15-C15', C11-C12, and C9-C10 were detected, but cleavage of the C11-C12 double bond predominated. Even better regioselectivity at this position was observed for cross-metathesis between beta-carotene and functionalized alkenes.

The cleavage of vitamin E galactoside in the rat tissue homogenates.

The stability of alpha-tocopheryl beta-galactoside in the presence of endogenous galactosidases in selected tissue homogenates (liver, kidney, ileum and brain) was estimated. High degree release of alpha-tocopherol from alpha-tocopheryl beta-galactoside in tissues of ileum, kidney and brain was observed (82%, 75% and 72%, increase above endogenous alpha-tocopherol, respectively). A possible enzymatic mechanism of the galactoside decomposition was proposed.

Treatment of cutaneous T-cell lymphomas with purine analogues (fludarabine and 2-chlorodeoxyadenosine).

PURPOSE: The aim of this study was to evaluate the efficacy and toxicity of the purine analogues 2-chlorodeoxyadenosine (2-CdA) and fludarabine (FAMP) combined with cyclophosphamide (CY) in the treatment of stage III and IV cutaneous T-cell lymphoma (CTCL). PATIENTS AND METHODS: From January 1998 to December 2002, 10 heavily pretreated patients with CTCL, hospitalized at the Department of Dermatology in Wroclaw, were administered monotherapy with 2-CdA (6 patients) or FAMP plus CY combination chemotherapy (4 patients). 2-CdA was administered at a dose of 0.12 mg/kg daily for 7 days every 28 days. FAMP was administered at a dose of 25 mg/m(2) daily, days 1-3, and cyclophosphamide 400 mg/m(2), day 1. The combination was repeated every 28 days. RESULTS: Five out of 6 patients treated with 2-CdA showed a transient partial remission of the skin lesions lasting for a median of 2 months, and 1 patient showed disease progression with dissemination of the skin lesions. Of the 4 patients who received FAMP plus CY 1 achieved complete remission lasting for 6 months, and 2 attained a partial response lasting for a median of 3 months. CONCLUSION: Purine analogues such as 2-CdA and FAMP may be used in the treatment of advanced stages of CTCL. The combination of FAMP plus CY, based on the restrictive effect of FAMP on the repair mechanisms of DNA damaged by CY, seems to be a promising therapeutic modality. Decreased immunity, leucopenia, thrombocytopenia and anaemia are common side effects of 2-CdA and FAMP.

Effect of repeated treatment with tianeptine and fluoxetine on central dopamine D(2) /D(3) receptors.

Tianeptine (TIA) is an antidepressant drug that has been shown to decrease extracellular serotonin level and reveals no affinity for neurotransmitter receptors. The present study was aimed at determining whether repeated TIA treatment induced any adaptive changes in the central dopamine D(2)/D(3) system (behavioural and biochemical) similar to those reported earlier for tricyclic antidepressants. Experiments were carried out on male Wistar rats. TIA was administered at a dose of 5 and 10 mg/kg once or repeatedly (twice daily for 14 days). Fluoxetine (FLU), used as a reference compound, was also administered at a dose of 10 mg/kg. The results obtained showed that TIA or FLU administered repeatedly increased the hyperlocomotion induced by D-amphetamine and 7-hydroxy-dipropylaminotetralin (7-OH-DPAT). Biochemical study revealed a decrease in the [(3)H]7-OH-DPAT binding sites after acute and repeated treatment with TIA or FLU in the islands of Calleja minor, as well as in the shell part of nucleus accumbens septi. On the other hand, both TIA and FLU administered repeatedly increased the binding of [(3)H]quinpirole (a D(2)/D(3) receptor agonist) in the nucleus caudatus as well as in the core part of the nucleus accumbens septi. Similar effects have been observed when dopamine D(2)/D(3) receptors were visualized with the use of [3H]raclopride, a dopamine D(2)/D(3) receptor antagonist. However, TIA and FLU induced a decrease in the level of mRNA encoding for dopamine D(2) receptors, not only after repeated but also after acute treatment. These results indicate that repeated TIA and FLU administration induces adaptive changes in the dopaminergic D(2)/D(3) system and especially enhances the functional responsiveness of dopamine D(2) and D(3) receptors. However, the question of whether this increased responsiveness is important for clinical antidepressant efficacy remains open.

Effect of repeated treatment with mirtazapine on the central alpha1-adrenergic receptors.

Mirtazapine (MIR) is an antidepressant which enhances noradrenergic and serotonergic 5-HT1A neurotransmission via antagomism of central alpha2-adrenergic autoreceptors and heteroreceptors. The drugs does not inhibit noradrenaline and serotonin reuptake but blocks the 5-HT, and 5-HT3 receptors and has high affinity only for central and peripheral histamine H1 receptors. The present study was aimed at determining whether repeated MIR treatment induced adaptive changes in the alpha1-adrenergic receptors, similar to those reported by us early for tricyclic antidepressants, The experiments were carried out on male mice and rats. MIR was administered at a dose of 10 mg/kg once or repeatedly (twice daily for 14 days). The obtained results showed that MIR administrated repeatedly potentiated the methoxamine- induced exploratory hyperactivity in rats and clonidine-induced aggressiveness in mice, those effects being mediated by alpha1-adrenergic receptors. MIR given repeatedly (but not acutely) increased the binding (Bmax ) of [3H]prazosin to alpha1-adrenergic receptors in cerebral cortex, however, the ability of the alpha1-adrenoceptor agonist phenylephrine to compete for the these sites was not significantly changed. The above results indicate that repeated MIR administration increases the responsiveness of alpha1-adrenergic system (behavioural and biochemical changes), as tricyclics do. However, the question whether the increased functional responsiveness found in the present study is important for the clinical antidepressant efficacy, remains open.

Digital hearing aids and future directions for hearing aids.

In recent years many technical evolutions have been applied in hearing aids. In this paper differences between analog, programmable and fully digital hearing aids, the basic and supplementary functions of a hearing aid, and some important issues and future directions for digital hearing aids will be mentioned.

Three new derivatives of 3-amino-1,2-propanediol; their spectral properties and biological evaluation.

Three new derivatives of 3-amino-1,2-propanediol have been synthesized. Full assignments of signals in their 1H- and 13C-NMR spectra are given. The influence of these compounds on the cardiovascular system in the anaesthetized rat was examined. In contrast to CGP 12177 which induced a strong increase in heart rate and a slight increase in blood pressure, compounds 1, 2 and 3 x HCl at doses up to 1 micromol/kg and compound 3 at doses of 0.01 and 0.1 micromol/kg did not change the cardiovascular parameters. The highest dose of compound 3-1 micromol/kg caused a very short-lasting decrease in heart rate (by 14%) and in blood pressure (by 25%).

Effect of repeated treatment with tianeptine and fluoxetine on the central alpha(1)-adrenergic system.

Tianeptine (TIA) is an antidepressant drug which enhances the reuptake of serotonin but, in contrast to tricyclics, shows no affinity for neurotransmitter receptors. The present study was aimed at determining whether repeated TIA treatment induced adaptive changes in the alpha(1)-adrenergic system, similar to those reported by us earlier for tricyclic antidepressants. The experiments were carried out on male mice and rats. TIA was administered at a dose of 5 or 10mg/kg once or repeatedly (twice daily for 14 days) and fluoxetine (FLU), used as a reference compound, at a dose of 10mg/kg. The obtained results showed that TIA administered repeatedly potentiated the methoxamine- and phenylephrine (PHEN)-induced exploratory hyperactivity in rats and clonidine-induced aggressiveness in mice, the effects mediated by alpha(1)-adrenoceptors. TIA given repeatedly (but not acutely) increased the binding (B(max)) of alpha(1)-adrenergic receptors in cerebral cortex for [(3)H]prazosin. However, the ability of the alpha(1)-adrenoceptor agonist PHEN to compete for these sites was not significantly changed. The above results indicate that repeated TIA administration increases the responsiveness of the alpha(1)-adrenergic system (behavioural and biochemical changes). On the other hand, FLU did not affect any behavioural and biochemical changes in this system.