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.

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.

Anti-Co3 and severe hemolytic disease of the newborn.

Irregular antibodies have been described to cause hemolytic disease of the newborn of varying severity. A case of anti-Colton 3 causing moderate to severe hemolysis in the newborn in two pregnancies is described. Only two cases of hemolytic disease of the newborn have been previously described; these resulted in mild hemolysis. The management of the condition is reviewed in the light of the current management of hemolytic disease of the newborn.

[Out-patient care in the structure of psychiatric institutions]. / Oddzial dzienny w strukturze instytucji psychiatrycznych.

The authors present models of functioning of hospital and out-patient psychiatric institutions, the problems faced in working together of the day treatment centre with other psychiatric institutions with special regard for the in-patient ward. The paper presents applied strategies of cooperation.

[Current views of the mechanism of action of antidepressants]. / Aktualne poglady na mechanizm dzialania leków przeciwdepresyjnych.

Considering the ever growing number of new discoveries and changes in ideas in the field of psychopharmacology, the authors present the actual state of knowledge about the mechanism of action of antidepressant drugs. Three periods characterize the research and the development of antidepressants. In the first period the presynaptic monoamine neuron was considered as the target structure both with respect to the search for the origin of depression and the mechanism of action of antidepressants. Two types of antidepressants, monoamine uptake inhibitors and monoamine oxidase inhibitors (IMAO) are representative of this period. In the second period, the research focused its interest primarily on monoaminergic receptors, anticipating that they were critically involved in the pathophysiology of depression. Such research sought to explain the antidepressant properties of iprindole and mianserine which are neither monoamine uptake inhibitors nor inhibitors of MAO. The onset of the third period is recent and it is characterized by the shift in research emphasis to intracellular transmission events. This period started with the discovery of the antidepressant properties of the phosphodiesterase inhibitor rolipram.

[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.

[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.

[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.

[Marital problems in depressive patients: a review of the literature and own clinical investigations]. / Problematyka malzenska pacjentów depresyjnych--przeglad literatury i badania wlasne.

The study presents a review of the literature and our own findings on marital and social problems of patients with major depression, and their spouses. The impact of illness on family and social life is marked and includes restrictions in social and leisure activities, considerable strain on marital relationships, lack of support. The functional impairment in families of depressed patients is an important factor worsening the course of the illness. These data suggest that in the complex treatment of depression a focus on intervention and prevention in areas of family and marital life is desirable.

[Appraisal of social situation of patients with endogenous depression]. / Ocena sytuacji spolecznej pacjentów leczonych z powodu depresji endogennej.

This study presents the appraisal of social situation of male and female patients with endogenous depression in follow-up.

[Relationships in families of depressed patients]. / Relacje w rodzinach generacyjnych pacjentów depresyjnych.

There is evidence that many depressed adults come from dysfunctional families. What dominates in our sample of patients treated for endogenous depression is adverse early family environment, especially relationship with father. Mother is described as hopeless and overprotective. Such description of a patient's family may cause--according to the cognitive model of depression--dysfunctional thinking style.

[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.

[Sexual dysfunctions in depressed patients]. / Zaburzenia seksualne u pacjentów depresyjnych.

Sexual dysfunction in depressed patients is an important clinical problem. Its complex etiology involves depressive symptoms, comorbid medical disorders, medication, difficulties in interpersonal relationships with partner, level of sexual functioning prior to the onset of illness. Also, mechanisms of action of psychotropic medication on sexual function are complex. Sexual dysfunction is a source of additional suffering for depressed patients and may contribute to poor compliance with treatment. It is an important challenge for the therapy of depression.

[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.

[Clinical pharmacokinetics of tricyclic antidepressants Part II. Drug therapy monitoring]. / Farmakokinetyka kliniczna trójpierscieniowych leków przeciwdepresyjnych Czesc II. Terapia monitorowana.

Large interindividual variation in steady-state TCA plasma concentrations, the presence of active metabolites, narrow therapeutic range and life-threatening results of TCA overdosage constitute indications for therapeutic drug monitoring. Conditions which must be fulfilled in order that serum concentration measurements may be taken into consideration in routine practice were discussed. The most important ones are: relationship between TCA concentration and antidepressant effect, the knowledge of therapeutic TCA range and availability of rapid and sensitive analytical method. Pharmacokinetic methods of TCA dosage individualization were also described. TCA serum concentration monitoring and dosage individualization of these drugs allows the clinician to optimize treatment of depression.

[Clinical pharmacokinetics of tricyclic antidepressants. Part I. Pharmacokinetic properties]. / Farmakokinetyka kliniczna trójpierscieniowych leków przeciwdepresyjnych. Czesc I. Wlasciwosci farmakokinetyczne.

Pharmacokinetic properties of tricyclic antidepressants (TCA) and factors changing pharmacokinetics of these drugs were presented. The following factors were discussed: age, genetically determined rate of metabolism and TCA interaction with co-administered drugs. As a consequence of these factors alterations mainly in elimination of TCA are observed. It leads to large interindividual variation in TCA plasma concentrations and lack of correlation between TCA concentration and dosage.

[Children and parental depression. An investigation on adult offspring of depressed patients]. / Dzieci wobec depresji rodziców. Wyniki badan nad doroslymi potomkami pacjentów depresyjnych.

The aim of our study was to assess the perception of parental depression by their adult offspring. Twenty nine offsprings aged 22.5 +/- 3.9 years were examined with the use of Parental Bonding Instrument, Beck Depression Inventory, Resenberg Scale, Hopelessness Scale, Automatic Thoughts Questionnaire and our own semistructured inventory. The offsprings of depressed patients reported negative impact of the illness on various aspects of life, especially when mother was ill. Surprisingly, the offsprings did not reveal disturbances in their thinking style, neither did they have depressive symptoms.

[Religiosity and intensity of endogenous depression symptoms. A follow-up study]. / Religijnosc a nasilenie objawów depresjii endogennej. Badania katamnestyczne.

The aim of our study was to determine if the quality of remission in unipolar affective disorder correlates with patient's religiosity. We have investigated 63 patients who were hospitalised in the Department of Psychiatry CMUJ between 1991 and 1997. The quality of remission has been assessed by Beck Depression Inventory (BDI), Rosenberg Self-esteem Scale (RS), Automatic Thoughts Questionnaire (ATQ), Hopelessness Scale (HS). Religiosity has been tested by the Scale of Individual Religiosity, and Religious Life Inventory. Patients were also assessed with the use of our own questionnaire, answering the following questions: 1. Do you believe?, 2. Does the disease influence the faith?, 3. Does your faith help in the disease?. Religiosity did not correlate with the quality of remission in depression in a statistically significant manner. There is only one statistically significant correlation: patients who answered positively the question number 3 (41 patients), have better remission. It is impossible to describe simple correlation between religiosity and remission in unipolar affective disorder. Patients who found their faith helpful have better remission.

[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.