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.

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.

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 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.

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.

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.

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.

Dihydropyridine calcium channel antagonists as antidepressant drugs in mice and rats.

A pharmacological profile of the effects of nimodipine, nifedipine and nitrendipine (2.5-20 mg/kg p.o.) in several models which are indicative of possible antidepressant activity, was tested in mice and rats. These compounds, as well as verapamil (short-lasting effect), but not diltiazem, reduced the hypothermia induced by a large dose of apomorphine in mice. Nimodipine and nifedipine slightly increased the behavioural action of L-DOPA in mice, and nimodipine facilitated the action of imipramine in the L-DOPA test. Nimodipine, nifedipine, verapamil and diltiazem slightly reduced the clonidine-induced hypoactivity in rats. The hypothermia induced by reserpine or clonidine in mice was not changed by these drugs. Various antidepressants (imipramine, amitriptyline, citalopram, mianserin) used in the behavioural despair test in mice, in doses which were not effective by themselves, increased the immobility-reducing effect when given jointly with 1,4-dihydropyridine calcium channel antagonists (5 mg/kg). The above results indicate that the psychopharmacological profile of nimodipine, nifedipine and nitrendipine resembles that of antidepressants in some tests only; moreover, these results support the assumption that concomitant administration of antidepressants and 1,4-dihydropyridine calcium channel antagonists may result in a greater antidepressant efficacy.

The effect of antidepressant drugs on the locomotor hyperactivity induced by MK-801, a non-competitive NMDA receptor antagonist.

It was found earlier that imipramine, amitriptyline and citalopram enhanced the locomotor hyperactivity induced by MK-801, a non-competitive NMDA receptor antagonist, in rats. Now, three other antidepressants: (+)-oxaprotiline, an inhibitor of the uptake of noradrenaline, (-)-oxaprotiline, an enantiomer devoid of any effect on the uptake of noradrenaline and fluoxetine, an inhibitor of the uptake of 5-hydroxytryptamine, have been examined in male Wistar rats. All those antidepressants, given in a single dose, increased the MK-801-induced locomotor hyperactivity. That increase was completely antagonized by haloperidol and partly by SCH 23390 and (+/-)-sulpiride; prazosin was inactive. Repeated administration of antidepressants produced a similar but more potent (than acute one) enhancement of the action of MK-801. Also, in that case haloperidol and SCH 23390 produced the strongest antagonistic effect; (+/-)-sulpiride and prazosin had a distinctly less potent action. Another effect of MK-801, anticonvulsant activity (electroshock-induced convulsions), was not increased by the antidepressants studied. These results indicate that antidepressants with a different pharmacological profile, increased the MK-801-induced locomotor hyperactivity, this effect being probably indirectly mediated, at least in part, by a dopamine mechanism.

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.

Activity of 72-kDa and 92-kDa matrix metalloproteinases in placental tissues of cows with and without retained fetal membranes.

This study compared the activity of matrix metalloproteinases (MMP-2 and MMP-9) in retained and non-retained bovine placenta. The activities of MMPs and their zymogens were measured in fetal and maternal placental tissues from control cows (group B) and animals affected with retention of fetal membranes (group A) using a zymography technique on 10 per cent SDS polyacrylamide gels. The activity of proMMP-9 detected only in the maternal part of the placenta was lower in group A than in group B. ProMMP-2 activity was higher in group A than in group B in both tissues. The active forms of MMP-2 were observed in the maternal and fetal part of placenta in group B, but only the 68-kDa form was detected in the placental tissues of group A. The differences in enzyme activity between the groups and the lack of 64- and 60-kDa active forms of MMP-2 in the maternal and fetal parts of the retained placenta may have influenced the hydrolysis of collagen and the proper release of fetal membranes.

Repeated treatment with imipramine potentiates the locomotor effect of apomorphine administered into the hippocampus in rats.

The effect of apomorphine, injected into the dorsal hippocampus, on the locomotor activity of imipramine-treated rats was studied. The rats were chronically implanted with cannulae 1 week before imipramine treatment. Imipramine was given in a dose of 10 mg/kg per os, acutely, or twice a day for 14 days. Intrahippocampal injection of apomorphine induced a dose-dependent increase in locomotor activity. This effect was antagonized by pretreatment with pimozide (2 mg/kg). Repeated, but not single, administrations of imipramine significantly enhanced the apomorphine-induced locomotor hyperactivity in rats. This effect was observed at 2, 48 and 96 h after the last dose of imipramine. The results obtained indicate that repeated administration of imipramine increases the responsiveness of the hippocampal dopaminergic system.

Comparison of the pharmacological actions of desmethylclomipramine and clomipramine.

This research compares the effects, in mice and rats, of desmethylclomipramine (DCLOM) and clomipramine (CLOM). DCLOM antagonized the hypothermia induced in mice by reserpine or apomorphine to a much greater extent than CLOM. Reserpine ptosis in mice was depressed by DCLOM only. Similarly, only DCLOM was effective in the behavioral despair test in rats. DCLOM increased the 5-hydroxytryptamine (5-HT) pressor effect in pithed rats, but to a lesser extent than CLOM by several factors. Only DCLOM increased the noradrenaline (NA) pressor effect. The depletion of NA induced by 6-hydroxydopamine was depressed by DCLOM only. The 5-HT depletion induced by p-chloromethamphetamine was antagonized only by CLOM. The results obtained show that the noradrenergic mechanism is of prime importance in the action of DCLOM and of much more importance than in the action of CLOM.

The central antiserotonergic action of mianserin.

The central antiserotonergic action of mianserin (MS) was tested in mice, rats, and rabbits. MS, like cyproheptadine, to which it was compared, inhibits the head-twitch response to 5-hydroxytryptophan in mice and rats without affecting the pinna reflex. MS does not change the flexor reflex of the hind limb of the spinal rat; it antagonizes its stimulation induced by fenfluramine, LSD, and quipazine, but not that induced by clonidine. The hyperthermia in rabbits caused by the serotonergic stimulants cited above is also antagonized by pretreatment with MS. Unlike cyproheptadine, MS is not active in the oxotremorine test. The results indicate that at low doses MS is a central serotonergic-receptor blocker.

Chronic treatment with some atypical antidepressants increases the brain level of 3-methoxy-4-hydroxyphenylglycol (MHPG) in rats.

We examined the effects of some atypical antidepressants with central antiserotonergic activity (mianserin, trazodone, danitracen, pizotifen), and 5-HT receptor blocking agents (cyproheptadine and metergoline), on whole rat brain levels of the main noradrenaline (NA) metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG). In acute experiments, when drugs were injected in a single dose 1, 2, 4, 24 or 48 h before decapitation, only mianserin elevated the MHPG level. In chronic experiments (drugs given b. i. d. for 3 weeks, the last dose being given 4 or 48 h before decapitation), all the drugs significantly increased the concentration of whole brain MHPG. The results indicate that chronic administration of atypical antidepressants leads to activation of the central NA system. It seems, with the exception of mianserin, that this is a secondary phenomenon, resulting from the antiserotonergic activity of the drugs. Our results further corroborate the existence of a serotonergic-noradrenergic interaction, consisting of an inhibitory influence of serotonin on the noradrenergic system.

The effects of paroxetine given repeatedly on the 5-HT receptor subpopulations in the rat brain.

Effects of paroxetine (10 mg/kg PO, twice daily, 14 days) on 5-HT receptor subpopulations in the brain were evaluated pharmacologically, electrophysiologically and biochemically in male Wistar rats. Imipramine was used for comparison. Repeated paroxetine antagonized the 8-OH-DPAT-induced behavioural syndrome (a 5-HT1A effect); imipramine showed similar, yet weaker, activity. The 5-HT-or 8-OH-DPAT-induced inhibition of population spikes in hippocampal slices was increased by both those repeated antidepressants. Repeated (or acute) paroxetine decreased the density of and increased the affinity for 5-HT1A receptors ([3H]-8-OH-DPAT used as ligand) in the hippocampus, while imipramine induced opposite effects. m-Chlorophenyl piperazine (m-CPP)-evoked exploratory hypoactivity, a 5-HT2C effect, was reduced by repeated paroxetine, but not by imipramine. Either of the antidepressants given repeatedly antagonized TFMPP-induced hyperthermia (another putative 5-HT2C effect). 5-HTP-induced head twitches (a 5-HT2A effect) were inhibited by repeated paroxetine or imipramine. Either antidepressant given repeatedly decreased the density of 5-HT2A receptors ([3H]-ketanserin as a ligand) in the brain cortex, but did not change their affinity. The present results indicate that paroxetine given repeatedly induces secondary changes in 5-HT2 receptors, which lead to reduction of the 5-HT2 neurotransmission (reduced responsiveness of 5-HT2 postsynaptic receptors). The consequences of the secondary changes in 5-HT1A receptors, found here still await clarification.

The influence of oxaprotiline enantiomers given repeatedly on the behavioural effects of d-amphetamine and dopamine injected into the nucleus accumbens.

The effects of (+)- and (-)-oxaprotiline, given repeatedly (10 mg/kg p.o., twice daily, 14 days), on the behavioural action of d-amphetamine and dopamine injected bilaterally into the nucleus accumbens were studied in rats. Repeated but not acute treatment with (+)- or (-)-oxaprotiline enhanced the d-amphetamine-induced locomotor hyperactivity. Both enantiomers, given repeatedly but not acutely, attenuated the inhibition of exploration activity induced by dopamine and potentiated the stimulating effect of dopamine as assessed in the open field test. The results indicate that, like other antidepressants studied previously, both oxaprotilines increase the responsiveness of the dopamine mesolimbic system (nucleus accumbens) of the rat.