Volume 64 (2017): Edizione 1 (September 2017)

Depressive disorder is one of the most common and serious psychiatric diagnosis in paediatric population, often connected with suicidal risk. In recent years, fluoxetine monotherapy is the gold standard in acute phase of depression treatment in children and adolescents, but is not effective enough after an acute phase of treatment. More helpful researches concerning more effective therapeutic strategies of depression in this age are insufficient. The aim of our study is to evaluate the effectiveness and safety of fluoxetine monotherapy in comparison with combined olanzapine/fluoxetine therapy in acute 6-week treatment of depression in adolescence. We found that combined therapeutic strategy, using olanzapine augmentation is predicted to be more useful in the treatment of adolescent depression.

The aim of the work was to find an experimental model suitable for the study of endothelial dysfunction induced by MS. We used hypertriglyceridemic rats (HTG) that were fed a hypercholesterolemic diet of different composition and duration: a 6-week administration of standard diet with an addition of cholesterol and fat (HTGChol) and a three-month administration of the same diet with an addition of fructose (HTGCholF). We investigated the effect of different diets on aortic endothelial function. The standard diet fed Wistar (W) and HTG rats served as controls. Decision for addition of fructose to HTGChol was done based on in vitro experiments evaluating the effect of high concentration of saccharide in the incubation solution on aortic endothelial function. This intervention caused significant deterioration of relaxation induced by acetylcholine (ACh). While in HTGChol, we did not find significant differences in the function of the aorta compared to W or HTG rats, adding of fructose to high fat diet and prolonging its administration resulted in significantly impaired endothelium-dependent relaxation. It seems that such a model is suitable for the study of endothelial dysfunction in MS and the effect of substances that may protect the endothelium.

Background: Fisetin, a derivate from the flavonol group may possess a variety of pharmacological effects. The aim of the presented study was to evaluate the bronchodilatory effect of fisetin after the acute or the chronic administration to guinea pigs with allergic airway inflammation.

Methods: Experimental animals were sensitized and challenged by ovalbumin. Fisetin was administered in dose 5mg/kg/p.o., either once after the end of 21-days sensitization or daily during the 21-days sensitization. By using the whole-body plethysmograph, we monitored the specific airway resistance, a parameter of airway hyperreactivity in vivo. The changes of the specific airway resistance were evaluated after the short-term inhalation of the bronchoconstriction mediator-histamine (10⁻⁶ mol.1⁻¹).

Results: Our results showed that the short-term as well as the long-term administration of fisetin caused decrease of the specific airway resistance values. The bronchodilatory effect of fisetin was comparable to the long-acting beta₂ sympathomimetic – salmeterol after the long-term administration. The measurements of the bronchodilatory activity after single administration have revealed more prolonged effect of fisetin comparing to the short-acting beta₂ sympathomimetic – salbutamol, as this remained even after the 5 hours, when salbutamol was already ineffective.

Conclusion: In conclusion, flavonol – fisetin has shown bronchodilatory potential. In the light of this fact, fisetin may represent potential substance that can be effective in both prevention as well as control of airway inflammation symptoms.

The present in vitro study was focused on the differences in expression and activity of calcium release-activated calcium (CRAC) channels of human term-pregnant and non-pregnant myometrium. The expression of Orai1 protein, as a functional subunit of CRAC channel, was significantly higher than in non-pregnant myometrium. Lower Orai1 protein expression did not influence the amplitude of contractile response of term-pregnant myometrium, but higher Orai1 expression observed in non-pregnant myometrium was related to the different influence of CRAC blocker on contraction frequency.

Vortioxetine is a novel antidepressant with two mechanisms of action – direct effect on several serotonin receptors and serotonin reuptake inhibition. Atypical antipsychotics, such as olanzapine, used in the augmentation of antidepressants causes not only a better response to treatment, but also increased number of remissions. The aim of our work was to evaluate the efficacy of vortioxetine monotherapy compared to the combined treatment vortioxetine and olanzapine in adult patients with depression during the acute phase of treatment lasting 6 weeks. Depressive symptomatology was assessed by the MADRS scale, anxiety symptoms were assessed by the HAM-A scale and global clinical impression were evaluated by the CGI-S scale. The number of patients in full-analysis set was 28. The results showed statistically significant improvement in CGI-S for both groups. Patients with vortioxetine monotherapy showed significant improvement in MADRS total score from the third week of treatment (p = 0.009) compared to patients with combined therapy that showed significant improvement since the end of first week of treatment (p = 0.036). Both groups showed significant improvement in HAM-A total score from the second week of treatment. Our results show the possibility of olanzapine in the augmentation strategy in treatment of major depressive disorder in adult patients.

Aim: N-acetylcysteine is the prototype of mucolytic agents. The aim of this study was to evaluate the acute and chronic effect of inhaled and oral N-acetylcysteine on airway reactivity, cough reflex and ciliary beat frequency and parameters of mentioned defense mechanisms were assessed in physiological conditions.

Methods: An experiment was performed using healthy guinea pigs treated with inhaled (0.6 M; 5min) and oral N-acetylcysteine (20 mg/kg), administrated either acutely as a single dose or chronically during 7 days. The cough reflex and specific airway resistance were assessed by in vivo method, using a double chamber plethysmograph box. The ciliary beat frequency was evaluated in in vitro conditions on tracheal brushed samples using light microscope coupled to high speed video camera.

Results: Inhaled and oral N-acetylcysteine, either administrated as a single dose or during 7 days, have shown a tendency to decrease sensitivity of the cough reflex and increase the airway reactivity. Acute administration of inhaled and oral N-acetylcysteine had no statistically relevant effect on the ciliary beat frequency, whereas chronic administration of both inhaled and oral N-acetylcysteine led to a marked reduction in the ciliary beat frequency.

Conclusion: Chronic administration of oral and inhaled N-acetylcysteine had a negative impact on the ciliary beat frequency, which represents one of the key factors determining the rate of mucociliary clearance. Thus, administration of N-acetylcysteine is less likely to increase the expulsion of mucus by ciliary movement. In addition, the observed tendency of inhaled and oral N-acetylcysteine to increase the airway reactivity may limit its use in conditions with severe airflow obstruction.

Blood pressure (BP) rhythm is exhibited in a circadian pattern regulated by complex system of endogenous factors. Administration of pharmacological treatment at the right time can influence the efficacy of treatment; but while kidneys play significant role in BP regulation, little is known about their role in chronopharmacotherapy. This study aimed to compare differences between morning and evening dosing with valsartan and amlodipine combination in both short-term and long-term settings and to elucidate the role of kidneys in chronopharmacology. Spontaneously hypertensive rats aged between 8 and 10 weeks were daily treated with 10mg/kg of valsartan and 4 mg/kg of amlodipine, either in the morning or in the evening with treatment duration of 1 and 6 weeks. After short-term treatment, only morning treatment group demonstrated significantly better outcomes in terms of BP control when compared to placebo. After long-term treatment, both treatment groups gained superior results in BP control against placebo; however, no significant difference was seen between morning and evening treatment. Interestingly, clock gene expression in kidney has been significantly modulated only in the evening-treated groups, with treatment intensifying the reduced Bmal1 levels, while Per2 expression was less altered. However, no direct relation with the outcomes of the therapy has been observed, suggesting that pharmacotherapy may serve as an independent modulator of peripheral circadian clock in the kidney.

Background: Degenerative spine disorders (DSD) are the most frequent reason of morbidity in adults. Commonly DSD includes degenerative disorders of intervertebral discs (IVDs), spinal stenosis and degenerative spondylolisthesis (SL). There is increasing evidence about significant role of cytokines in DSD pathogenesis, symptomathology and progression, but their protective levels remain still unknown.

Material and Methods: The aim of presented study was to provide quantitative and qualitative analysis of cytokine, chemokine and growth factors levels in individual parts of IVDs - annulus fibrosus (AF) and nucleus pulposus (NP) - separately and in facet joints (FJ) subchondral bone of patients with DSD and in controls - healthy subjects during a multiorgan procurement procedure. Bio-Plex^® assay was used to measure concentrations of 27 different cytokines in tissue of patients with DSD. Their concentrations in tissues of healthy subjects during a multiorgan procurement procedure represented protective levels.

Results: The Bio-Plex^® assay revealed significant differences between the patients suffered from degenerated and herniated IVDs and from lumbar SL and controls in cytokines, chemokines and growth factor profiles suggested that pro-inflammatory changes of both NP and AF were dominated in herniated IVDs, whereas the same tissue of lumbar SL patients exhibited much more complex changes in cytokine levels suggested o only ongoing inflammation (IL-6, IL-8, MCP-1, TNF-α), abut also antiinflammatory processes (IL-ra, IL-10) or connective tissue remodeling (PDGF-bb, IL-17, VEGF). The different mediators were found elevated in lumbar SL samples of subchondral FJ bone. These also confirmed ongoing inflammation, accelerated bone resorption and formation and increased fibroblasts activity in FJ bone.

Conclusion: The study supported the significant involvement of several cytokines, chemokines and growth factors in the pathogenesis of DSD. These cytokines should represent future potential targets for new biological treatment able to slow DSD progression as well as factor determining prognosis of DSD.