Dramatic slowing down of the conformational equilibrium in the silyl derivative of glucose in the vicinity of the glass transition temperature.

The vitrification process is usually preceded by a significant change (around 6-8 decades) in the viscosity, structural relaxation times, or diffusion that occurs in a relatively small range of temperatures in fragile liquids. Along with this phenomenon, conformations of the molecules vary as well. In fact, this process is studied in bulk polymers and high molecular weight materials deposited in the form of thin films. On the other hand, spatial rearrangement of small glass formers in the supercooled liquid state has not been intensively investigated, so far. Herein, data obtained from measurements carried out using various experimental techniques on supercooled 1,2,3,4,6-penta-O-(trimethylsilyl)-d-glucopyranose (S-GLU) have revealed that rotations of silyl moieties along with the deformation in the saccharide ring are significantly slowed down in the vicinity of the glass transition temperature (Tg). These intramolecular reorganizations affect the structural relaxation time, atomic pair distribution function, integrated intensity, as well as a number of bands and signals observed, respectively, in the Raman and NMR spectra. Data reported herein offer a better understanding of the conformational variation and time scale of this process in the complex and flexible molecules around the Tg.

Studying molecular dynamics of the slow, structural, and secondary relaxation processes in series of substituted ibuprofens.

In this paper, the molecular dynamics of a series of ester derivatives of ibuprofen (IBU), in which the hydrogen atom from the hydroxyl group was substituted by the methyl, isopropyl, hexyl, and benzyl moieties, has been investigated using Broadband dielectric (BD), Nuclear magnetic resonance (NMR), and Raman spectroscopies. We found that except for benzyl IBU (Ben-IBU), an additional process (slow mode, SM) appears in dielectric spectra in all examined compounds. It is worth noting that this relaxation process was observed for the first time in non-modified IBU (a Debye relaxation). According to suggestions by Affouard and Correia [J. Phys. Chem. B. 114, 11397 (2010)] as well as further studies by Adrjanowicz et al. [J. Chem. Phys. 139, 111103 (2013)] on Met-IBU, it was attributed to synperiplanar-antiperiplanar conformational changes within the molecule. Herein, we have shown that with an increasing molecular weight of the substituent, the relaxation times of the SM become longer and its activation energy significantly increases. Moreover, this new relaxation mode was found to be broader than a simple Debye relaxation in Iso-IBU and Hex-IBU. Additional complementary NMR studies indicated that either there is a significant slowdown of the rotation around the O=C-O-R moiety or this kind of movement is completely suppressed in the case of Ben-IBU. Therefore, the SM is not observed in the dielectric loss spectra of this compound. Finally, we carried out isothermal experiments on the samples which have a different thermal history. Interestingly, it turned out that the relaxation times of the structural processes are slightly shorter with respect to those obtained from temperature dependent measurements. This effect was the most prominent in the case of Hex-IBU, while for Ben-IBU, it was not observed at all. Additional time-dependent measurements revealed the ongoing equilibration manifested by the continuous shift of the structural process, until it finally reached its equilibrium position. Further Raman investigations showed that this effect may be related to the rotational/conformational equilibration of the long hexyl chains. Our results are the first ones demonstrating that the structural process is sensitive to the conformational equilibration occurring in the specific highly viscous systems.

Specific interactions between Smad proteins and AP-1 components determine TGFß-induced breast cancer cell invasion.

Deregulation of the transforming growth factor ß (TGFß) signal transduction cascade is functionally linked to cancer. In early phases, TGFß acts as a tumor suppressor by inhibiting tumor cell proliferation, whereas in late phases, it can act as a tumor promoter by stimulating tumor cell invasion and metastasis. Smad transcriptional effectors mediate TGFß responses, but relatively little is known about the Smad-containing complexes that are important for epithelial-mesenchymal transition and invasion. In this study, we have tested the hypothesis that specific members of the AP-1 transcription factor family determine TGFß signaling specificity in breast cancer cell invasion. Using a 3D model of collagen-embedded spheroids of MCF10A-MII premalignant human breast cancer cells, we identified the AP-1 transcription factor components c-Jun, JunB, c-Fos and Fra1 as essential factors for TGFß-induced invasion and found that various mesenchymal and invasion-associated TGFß-induced genes are co-regulated by these proteins. In situ proximity ligation assays showed that TGFß signaling not only induces complexes between Smad3 and Smad4 in the nucleus but also complexes between Smad2/3 and Fra1, whereas complexes between Smad3, c-Jun and JunB could already be detected before TGFß stimulation. Finally, chromatin immunoprecipitations showed that c-Jun, JunB and Fra1, but not c-Fos, are required for TGFß-induced binding of Smad2/3 to the mmp-10 and pai-1 promoters. Together these results suggest that in particular formation of Smad2/3-Fra1 complexes may reflect activation of the Smad/AP-1-dependent TGFß-induced invasion program.

Oncolytic adenovirus modified with somatostatin motifs for selective infection of neuroendocrine tumor cells.

We have previously described the oncolytic adenovirus, Ad(CgA-E1A-miR122), herein denoted Ad5(CgA-E1A-miR122) that selectively replicates in and kills neuroendocrine cells, including freshly isolated midgut carcinoid cells from liver metastases. Ad5(CgA-E1A-miR122) is based on human adenovirus serotype 5 (Ad5) and infects target cells by binding to the coxsackie-adenovirus receptor (CAR) and integrins on the cell surface. Some neuroendocrine tumor (NET) and neuroblastoma cells express low levels of CAR and are therefore poorly transduced by Ad5. However, they often express high levels of somatostatin receptors (SSTRs). Therefore, we introduced cyclic peptides, which contain four amino acids (FWKT) and mimic the binding site for SSTRs in the virus fiber knob. We show that FWKT-modified Ad5 binds to SSTR2 on NET cells and transduces midgut carcinoid cells from liver metastases about 3-4 times better than non-modified Ad5. Moreover, FWKT-modified Ad5 overcomes neutralization in an ex vivo human blood loop model to greater extent than Ad5, indicating that fiber knob modification may prolong the systemic circulation time. We conclude that modification of adenovirus with the FWKT motif may be beneficial for NET therapy.

Azinyl sulfides--CXVIII. Antimicrobial activity of novel 1-methyl-3-thio-4-aminoquinolinium salts.

Synthesis and antimicrobial activity of novel 1-methyl-3-alkylthio-4-aminoquinolinium salts 2 and 1-methyl-3-acylthio-4-aminoquinolinium salts 4 are described. Compounds 2 were obtained by reacting 1-methyl-3,4-(dimethylthio)quinolinium chloride 1 with amines and by reacting 1-methyl-4-aminoquinolinium-3-thiolates 3 with alkylating agents. Compounds 4 were obtained by the reaction of 1-methyl-4-aminoquinolinium-3-thiolates 3 with acylating agents. Antimicrobial activity of compounds 2 and 4 was determined using G+ (Staphylococcus aureus, Enterococcus faecalis) and G(-) (Escherichia coli, Pseudomonas aeruginosa) strains as well as Candida albicans yeast. The compounds show greatest activity against S. aureus whereas the lowest against P. aeruginosa.

[Personality patterns in coronary artery disease]. / Cechy osobowosci a chrooba niedokrwienna serca.

Relation of personality patterns and type A behaviour to the risk and prognosis of coronary artery disease was described. The particular interest of researchers was directed toward hostility, which correlated with the course of coronary artery disease. Finally, therapeutical implications, deriving from the holistic approach to cardiological patients, were proposed.

[Zinc homeostasis and glutamatergic system in the pathogenesis and treatment of depression]. / Homeostaza cynku i uklad glutamatergiczny w patogenezie i terapii depresji.

This article presents a review of the interactions between zinc and glutamate system in the pathophysiology and treatment of depression.

[A trial for the complex risk assessment of repeated suicide predictors in patients after suicidal poisoning attempts, hospitalized in the Department of Clinical Toxicology CM UJ in Krakow. I. Influence of socio-demographic factors]. / Próba kompleksowej oceny predyktorów ryzyka ponowienia samobójstwa u pacjentów po samobójczym zatruciu lekami, hospitalizowanych w Klinice Toksykologii CM UJ w Krakowie. Czesc I. Wplyw czynników socjodemograficznych.

The study included 180 patients aged 18-79 (average 36) hospitalized for suicide attempts (drug intoxication) in Department of Clinical Toxicology CMUJ from March to December 2000. Examined group was composed of 49 men and 131 women. Structured investigation and medical documentation were used to estimate crucial socio-demographic risk factors of repeated suicide attempt. The following socio-demographic traits were taken into consideration in analysis: age, sex, marital status, place of living, education, employment, family background. We distinguished among patients under examinations: patients after first suicide attempt (I) and group after another suicidal attempt (II). The second group consisted of 15 men (27.8% of the total) and 39 women (72.2% of the total). Young people under 30 constituted 37.2% of the whole examined population. In population of women after repeated suicide attempt the percentage of divorced ones increased considerably (from 2.2% to 10.2%). Both in men and women after repeated suicide attempt the percentage of persons with only elementary education increased (from 34.1% to 53.7%). We observed high unemployment rate (from 26.6% to 29.6%) in both groups. Percentage of pensioners increased from 23.5% after first suicidal attempt to 33.3% after repeated suicidal attempt in men and from 25.5% to 35.9% in women. Men after repeated suicide attempt more often live with their parents, while women from the second group more often live alone with their children. It seems that some of the analysed predictors which are expression of social unadjustment may make risk factor for repeated suicidal attempts.

[A trial for the complex risk assessment of repeated suicide predictors in patients after suicidal poisoning attempts, hospitalized in the Department of Clinical Toxicology CM UJ in Krakow. II. Clinical predictors]. / Próba kompleksowej oceny predyktorów ryzyka ponowienia samobójstwa u pacjentów po samobójczym zatruciu lekami, hospitalizowanych w Klinice Toksykologii CM UJ w Krakowie. Czesc II. Predyktory kliniczne.

The study included 180 patients aged 18-79 (average 36) hospitalized for suicide attempts (drug intoxi-cations) in the Department of Clinical Toxicology CM UJ from March to December 2000. Examined group was composed of 49 men and 131 women. The following tests were used in this study: structured questionnaire, psychological tests: Beck Depression Inventory, Hamilton Depression Scale, Hopelessness Scale, Suicidal Intent Scale, Life Events Scale, SOC 29 (by Antonovsky). Besides, we used data from patients' history. The aim of our study is to analyse clinical data of suicidal attempters--after first and repeated suicidal attempts. We took into consideration the severity of coma, severity of intoxication, the kind of substances used in the attempt, the presence of alcohol, previous psychiatric treatment, cases of suicide among the patients' close friends or relatives and duration of hospitalization. Then the psychiatric diagnosis was stated. The analysis of severity of intoxication (divided into three stages: severe, moderate, and light according to the Poisoning Severity Score (PSS) indicated that in the group of repeated suicide attempters the percentage of severe intoxications was greater (9.2%) then in first time attempters. In the population of second time female attempters there is a greater percentage of persons who took neuroleptics (15.4%) compared to group first attempters (5.4%). In both groups the majority were taking anxiolytisc, sleep-inducing and mixed drugs. There was a greater percentage of persons drinking alcohol during the attempt among repeated suicidal attempters (38.8%) than among the first time attempters (26%). The percentage of persons with diagnosis of mental disease (treated in ambulatory or in hospital) is higher in the group of repeated suicide attempters (25.9%) then after first attempters (6.3%). In both groups a lot of persons had reactive depression, often associated with personality disorders, rarely endogenic depressions or psychosis. We observed that addiction to alcohol is often a problem in men who attempt suicide (I group--32.3%, II group--33.3%). The analysis of medical documentation indicated in the group of repeated suicide attempters a high percentage of people with cases of suicide among their close friends or relatives.

[An episode of depression in a patient with coronary artery disease]. / Przypadek depresji u pacjentki z choroba niedokrwienna serca.

An episode of depression in a patient with Ischaemic Heart Disease is presented. The patient had undergone coronary angioplasty with optimal results. The clinical picture of the depressive disorder consisted mainly of chest pain complaints in the cardiac area, which made the diagnosis all the more difficult. The application of antidepressive treatment caused the depressive symptoms together with the chest pain to disappear. A therapeutic success was achieved owing to the good co-operation between the invasive cardiologist and the psychiatrist.

[Sexual dysfunction during treatment of depression]. / Dysfunkcje seksualne w przebiegu leczenia przeciwdepresyjnego.

Sexual dysfunction in depressed patients is an important clinical problem. Its etiology is complex, however pharmacotherapy is one of the most important factors. It is important for therapists to consider effects of antidepressants on sexual functions in planning treatment strategy.

[Sexual functioning of patients with major depression. Pilot study]. / Funkcjonowanie seksualne pacjentów depresyjnych. Badanie pilotazowe.

Disturbances in sexual functioning in patients with endogenous mental disorders are frequently reported. The aim of the study was to estimate the occurrence of sexual disfunctions in patients hospitalised for major depression (unipolar affective disorder). The investigations covered 53 persons remaining in stable partnership. Apart from the assessment of psychological state, depressive symptoms and the course of treatment, we analysed the quality of relations with the partner, sexual satisfaction, willingness to and frequency of sexual intercourse, satisfaction with oneself as a sexual partner. The obtained results indicate that sexual problems must not be neglected in treatment of depressive patients.

[Transcranial magnetic stimulation versus electroconvulsive shocks: neuroanatomical investigations in rats]. / Przezczaszkowa stymulacja magnetyczna a zabiegi elektrowstrzasowe--badania neuroanatomiczne u szczura.

Since the time of introducing ECT to the clinical practice, the method always raised questions regarding possibility that the current running through structures of a brain may evoke structural changes and, as a result, evoke convulsive attacks. Pathological changes (swelling, gliosis, atrophy, necrosis) were observed most often after "mega"--schemes including series of several to several hundred ECT treatments. Regime used nowadays including only 8-12 ECT sessions seems to be entirely safe. There are, however, only a few experimental works dealing with this problem. In 1992 research started on a new neurophysiological technique--transcranial magnetic stimulation (TMS) in depression. The advantage of this method is that is does not seem to evoke convulsive attacks. Prolonged rapid rate TMS (rTMS) seems to be particularly efficient in treatment of depression. Despite thousands of works describing various functional effects of TMS, there are obviously no researches on structural effects of the technique. In the case of experimental research on animals a few works were published and their results seem to be ambiguous. We have examined the influence of prolonged repetitive rTMS (B = 1.4 T, t = 5.5 min, f = 30 Hz), and standard ECT (I = 150 mA, t = 0.5 s, f = 50 Hz) on the structure of brain tissue in rats. Both groups of animals (n = 10) received 12 stimulation sessions. After the treatment the animals were routinely processed for electron microscopy (EM) and for light microscopy (LM). Our investigations suggest that the technique of ECT shows a considerable neurotoxic potential. In comparison to ECT--the rTMS method seems to be more safe.

Plasma levels of interleukin-6, interleukin-10, and interleukin-1 receptor antagonist in depression: comparison between the acute state and after remission.

There is now some evidence that major depression is accompanied by an immune response with an increased production of pro-inflammatory cytokines. The aim of the present study was to examine serum level of cytokines: interleukin-6 (IL-6), which is considered pro-inflammatory one and anti-inflammatory cytokines: interleukin 10 (IL-10), and interleukin-1 receptor antagonist (IL-1Ra) in acute clinical state of depression and after 6-week antidepressant treatment. Serum IL-6, IL-10, IL-1Ra levels were higher in the subjects with major depression than in normal controls although these results were not statistically significant. The mean score according to the Hamilton Depression Rating Scale (HDRS) in the patients significantly decreased during the 6 weeks of the study, demonstrating an overall improvement. Successful antidepressant treatment had no significant effect on serum level of this cytokines.

[Depressive disturbance and quality of life in patients with coronary artery disease]. / Zaburzenia depresyjne a jakosc zycia u pacjentów z choroba niedokrwienna serca.

The aim the study was to evaluate the impact of mood disturbances on the subjective quality of life in patients with coronary artery disease after an effective angioplasty. The study covered 100 patients with the optimum result of PTCA. Their condition was evaluated one day before and four weeks after angioplasty. Significant differences in the subjective quality of life assessment were detected depending on the occurrence and dynamics of depressive symptoms. The authors postulate evaluation of psychological state and introduction of anti-depressive therapy in patients with coronary artery disease subjected to revascularisation.

[Development and application of cognitive therapy in affective disorders]. / Rozwój i zastosowanie terapii poznawczej w chorobach afektywnych.

Cognitive psychotherapy was originally created for out-patient treatment of mild and moderate, non-psychotic, unipolar depressive disorder. Further development of the therapy resulted in its use in various mental disorders. Cognitive therapy has also been used in wide spectrum of affective disorders, including severe, endogenous depression, chronic depression, bipolar disorder and suicidality. Therapeutic programs involve individual, group, family and marital cognitive psychotherapy. Effectiveness and clear conceptualization encourages to wide use of this kind of therapy.

[The behavioral effects of the transcranial magnetic brain stimulation in rat: the comparison with electroshock]. / Efekty behawioralne przezczaszkowej stymulacji magnetycznej (rTMS) u szczura: porównanie z zabiegami elektrowstrzasowymi.

The few experimental studies suggest that repetitive rapid-rate transcranial magnetic stimulation (TMS) evokes in the brain functional and structural changes similar to those evoked by electroconvulsive therapy (ECT). The aim of the present work was to compare the influence of the repetitive TMS (B = 1.6 T; f = 20 and 30 Hz; t = 5 and 5.5 minutes; N = 9 and 18 days) and that of ECT (I = 150 mA; f = 50 Hz; t = 0.5 s; N = 9 days) on rats' behaviour in the tests of free field, tail flick, motor hyperactivity after administration of apomorphine and in forced swimming. None of the rats subjected to TMS suffered from convulsive attack, which followed every electroconvulsive shock. In the free field test it was detected that neither TMS nor ECT applied individually or repetitively disturbed general motor activity of rats. Repetitive electroconvulsive shocks caused analgesia, prolonging the latency of tail flick by 46% (p < 0.001). Moreover, the tail flick test revealed hyperalgesia in the rats subjected to TMS (24 and 21% of control values respectively; p = 0.05). Motor hyperactivity of rats stimulated with administration of apomorphine was intensified both by TMS (by 58% at maximum in the 30th minute of the experiment; p = 0.001) and, all the more, by ECT (by 92% at maximum at the end of the test; p = 0.01). In the forced swimming test, the greatest decrease of inertia period was observed ECT--up to 50% of control values (p = 0.001). TMS had weaker effects--the decrease amounted to 29% of control values (p = 0.01). The shortening effect depended on the parameters of TSM. The obtained results seem to confirm that TMS, like ECT, evokes in rats certain reactions suggesting its antidepressive action, but causes less undesirable effects.

Zinc exhibits an antidepressant-like effect in the forced swimming test in mice.

The effects of zinc, the NMDA receptor inhibitor, were studied in the forced swimming (Porsolt's) test in mice. Zinc (ZnSO4) at a dose of 30 mg/kg (but not at a dose of 10 mg/kg), similarly to imipramine (30 mg/kg), reduced the immobility time in that test. Moreover, zinc at both doses reduced the locomotor activity. The obtained results indicate that zinc induces an antidepressant-like effect in the forced swimming test. Since zinc reduces the locomotor activity, this antidepressant-like effect is not related to the alteration of general activity.

[Pharmacotherapy for depression in patients with myocardial ischemia]. / Farmakoterapia depresji u pacjentów z choroba niedokrwienna serca.

The comorbidity of depression and heart diseases is an important but still devaluated clinical problem. Mood disorders in those ill with cardiac ischaemic disease significantly worsen the predictive mortality and quality of life. It may be predicted that adequate therapy of depression could have a positive effect on the long term course of IHD. Careful analysis of indications and contradictions as well as the application of new generation drugs allows for safe therapy. Evident benefits of appropriate treatment of depression in this group of patients, deny the old thesis on the damage of antidepressive drugs on the cardio-vascular system.

[Depression in coronary artery disease]. / Depresja w chorobie niedokrwiennej serca.

Comorbidity of major depression and cardiac disorders is an important, however undervalued clinical problem. Cardiac mortality in patients with affective disorders is higher in comparison to general population. On the other hand, in people with coronary artery disease coexistence of depressive syndrome significantly worsens mortality rate as well as quality of life. Major depression in cardiological patients is rarely adequately diagnosed and even more seldom treated. It could be suggested that adequate treatment of major depression could improve long-term prognosis in coronary artery disease.