Search

Cel pracySkuteczność wortioksetyny w leczeniu depresji jednobiegunowej oceniano w wielu badaniach, brakuje jednak prób weryfikujących skuteczność wortioksetyny w depresji w przebiegu choroby afektywnej dwubiegunowej (ChAD).MetodaW grupie 60 pacjentów z depresją w przebiegu ChAD do wcześniej stosowanego leczenia normotymicznego (LN) dołączano wortioksetynę w dawce 10-20 mg/d w ramach 24-tygodniowej naturalistycznej próby otwartej. Do najczęściej stosowanych LN należały lamotrygina, kwetiapina, olanzapina i sole kwasu walproinowego. Skuteczność terapii oceniano podskalami Poprawy i Ciężkości Skali Ogólnego Wrażenia Klinicznego (CGI-I i CGI-S). Pacjentów klasyfikowano jako osiągających odpowiedź na leczenie wortioksetyną, jeżeli uzyskali wynik 1 lub 2 punktów w skali CGI-I. Za kryterium remisji przyjęto osiągnięcie wyniku 1 w skali CGI-S.Wyniki73% pacjentów (44/60) osiągnęło odpowiedź na leczenie wortioksetyną, a 52% (31/60) spełniło kryteria remisji klinicznej objawów depresyjnych (po czasie: 8,97±4,05 tygodni). Nie obserwowano znamiennych zależności pomiędzy odsetkami odpowiedzi na leczenie/remisji w następstwie stosowania wortioksetyny i jej dawką, typem ChAD, stopniem zaawansowania klinicznego ChAD, występowania szybkiej zmiany faz, historii występowania objawów psychotycznych, wybranych analizowanych objawów epizodu depresyjnego lub przyjmowanego równocześnie LN. 4 uczestników (6,7%) zrezygnowało z kontynuacji terapii z powodu doświadczanych działań niepożądanych (nudności), a 7 (11,7%) przerwało stosowanie wortioksetyny z powodu zmiany fazy ChAD. U 14 pacjentów (23%) doszło do utraty efektu terapeutycznego wortioksetyny po wcześniejszym osiągnięciu odpowiedzi terapeutycznej lub remisji.WnioskiWyniki wskazują na stosunkowo wysokie odsetki odpowiedzi na leczenie i remisji w toku 24-tygodniowego leczenia depresji dwubiegunowej wortioksetyną w połączeniu z LN. Powyższe dane mogą świadczyć, że leczenie kombinowane wortioksetyną i LN stanowi skuteczną i dobrze tolerowaną formę terapii depresji w przebiegu ChAD.

Cel pracyW odniesieniu do choroby afektywnej dwubiegunowej (ChAD), dotychczasowe prace wskazują na zaburzenia ruchów sakadycznych, głównie pod postacią wydłużenia czasu reakcji (latencji) w testach prosakad i antysakad. Dotychczas nie przeprowadzono oceny ruchów wergencyjnych gałek ocznych u osób z ChAD. Głównym celem naszego badania jest ocena parametrów konwergencji (zbieżne ruchy gałek ocznych) w tej grupie klinicznej.MetodaDo badania włączono 30 pacjentów z ChAD w stanie remisji objawowej i 23 zdrowych ochotników. Uczestników poddano badaniu optometrycznemu oceniającemu punkt bliski konwergencji przy użyciu pręta fiksacyjnego. Badanie okulometryczne przeprowadzono przy pomocy okulografu wykorzystującego promieniowanie podczerwone z dedykowanym stymulatorem wergencji.WynikiPacjenci z ChAD wykazali istotnie większy średni błąd pozycji konwergencji do celu oraz większą liczbę wtrąceń sakadycznych w porównaniu do grupy kontrolnej. Analiza składowych głównych przeprowadzona na zmiennych okulometrycznych pokazała istotne różnice między pacjentami z ChAD a zdrowymi ochotnikami. Wykazano obecność istotnych korelacji między zaburzeniami ruchów wergencyjnych a liczbą wtrąceń sakadycznych.WnioskiPacjenci z ChAD ujawnili zaburzenia ruchów wergencyjnych gałek ocznych podobne do zaburzeń opisywanych w trakcie śledzenia bodźców poruszających się w płaszczyźnie czołowej. Podczas gdy zaburzenia wergencji były opisywane w innych zaburzeniach psychicznych, nasza praca po raz pierwszy obiektywnie zmierzyła to zjawisko w ChAD.

Magnocellular neurosecretory cells (MNCs) clustered in the hypothalamic paraventricular nucleus (PVN) and supraoptic nucleus constitute a major source of oxytocin (OXT) and arginine vasopressin (AVP) peptides, and are among the best described peptidergic neurons in the brain. OXT and AVP are involved in a range of homeostatic processes, social behaviours, emotional processes, and learning. Notably, their actions can be sex-specific, and several sex differences in the anatomies of the OXT and AVP systems have been reported. Nonetheless, possible sex differences in the detailed distributions of MNCs and in their intrinsic electrical properties ex vivo have not been extensively examined. We addressed these issues utilizing immunostaining and patch-clamp ex vivo recordings. Here, we showed that Sprague-Dawley rat PVN AVP neurons are more numerous than OXT cells and that more neurons of both types are present in males. Furthermore, we identified several previously unreported differences between putative OXT and AVP MNC electrophysiology contributing to their partially unique profiles. Notably, elucidation of the highly specific action potential (AP) shapes, with AVP MNCs having a narrower AP and faster hyperpolarizing after-potential (HAP) kinetics than OXT MNCs, allowed unambiguous discrimination between OXT and AVP MNCs ex vivo for the first time. Moreover, the examined electrophysiological properties of male and female MNCs generally overlapped with the following exceptions: higher membrane resistance in male MNCs and HAP kinetics in putative OXT MNCs, which was slower in males. These reported observations constitute a thorough addition to the knowledge of MNC properties shaping their diverse physiological actions in both sexes.

Background: Schizophrenia (SZ) and bipolar disorder (BD) patients share deficits in motor functions in the form of neurological (NSS) and cerebellar soft signs (CSS), and implicit motor learning disturbances. Here, we use cluster analysis method to assess (1) the relationship between those abnormalities in SZ and BD and (2) the differences between those groups. Methods: 33 SZ patients, 33 BD patients as well as 31 healthy controls (HC) took part in the study. We assessed CSS with the International Cooperative Ataxia Rating Scale (ICARS) and NSS with the Neurological Evaluation Scale (NES). Implicit motor learning was evaluated with the Serial Reaction Time Task (SRTT). Participants were divided into clusters (Ward's method) based on the mean response time and mean error rate in SRTT. The difference in ICARS and NES scores, and SRTT variables between clusters were evaluated. We have measured associations between SRTT parameters and both ICARS and NES total scores and subscores. Results: Cluster analysis based on the SRTT parameters allowed to extract three clusters. Those were characterized by the increasing disruption of motor functioning (psychomotor retardation, the severity of NSS and CSS) regardless of the diagnosis. Cluster 1 covered almost all of HC and was characterized by faster reaction times and small number of errors. BD and SZ patients represented in cluster 1, although fully functional in performing the SRTT, showed higher rates of NSS and CSS. Patients with BD and SZ were set apart in clusters 2 and 3 in a similar proportion. Cluster 2 presented significantly slower reaction times but with the comparable number of errors to cluster 1. Cluster 3 consisted of participants with normal or decreased reaction time and significantly increased number of errors. None of the clusters were predominantly composed of the patients representing one psychiatric diagnosis. Conclusions: To our best knowledge, we are presenting the first data indicating the relationship between implicit motor learning and NSS and CSS in SZ and BD patients' groups. Lack of clusters predominantly represented by patients with the diagnosis of SZ or BD may refer to the model of schizophrenia-bipolar disorder boundary, pointing out the similarities between those two disorders.

Malformations of cortical development (MCDs), such as cortical dysplasia and tuberous sclerosis complex, are common causes of intractable epilepsy, especially in paediatric patients. Recently, mounting evidence points to a common pathology of these disorders. Hyperactivation of mammalian target of rapamycin (mTOR) has been proposed as a central mechanism in most, if not all, MCDs. The transition from mTOR hyperactivation and cellular abnormalities to large-scale functional changes and seizure is, however, not fully understood. In this article we set out to review currently available information regarding MCD pathology, focusing on glial cells - especially astrocytes - and their interactions with the brain vascular system. A large body of evidence points to these elements as potential targets in MCD. Here, we attempt to provide a review of this evidence and propose some hypotheses regarding the possible chain of events linking primary glial dysfunction and epilepsy. We focus on extracellular matrix remodelling, blood-brain barrier leakage and failure of astrocyte-dependent removal of extracellular debris. We posit that the failure of these systems results in a chronically pro-inflammatory environment, maintaining local astrocytes in a state of gliosis, with increased susceptibility to seizures as a consequence.

Stress elicits the release of glucocorticoids (GCs) that regulate energy metabolism and play a role in emotional memory. Astrocytes express glucocorticoid receptors (GR), but their contribution to cognitive effects of GC’s action in the brain is unknown. To address this question, we studied how astrocyte-specific elimination of GR affects animal behavior known to be regulated by stress. Mice with astrocyte-specific ablation of GR presented impaired aversive memory expression in two different paradigms of Pavlovian learning: contextual fear conditioning and conditioned place aversion. These mice also displayed compromised regulation of genes encoding key elements of the glucose metabolism pathway upon GR stimulation. In particular, we identified that the glial, but not the neuronal isoform of a crucial stress-response molecule, Sgk1, undergoes GR-dependent regulation in vivo and demonstrated the involvement of SGK1 in regulation of glucose uptake in astrocytes. Together, our results reveal astrocytes as a central element in GC-dependent formation of aversive memory and suggest their relevance for stress-induced alteration of brain glucose metabolism. Consequently, astrocytes should be considered as a cellular target of therapies of stress-induced brain diseases.

Bergmann glia (BG), a specific type of radial astrocytes in the cerebellum, play a variety of vital functions in the development of this structure. However, the possible role of BG in the development of abnormalities observed in individuals with autism spectrum disorder (ASD) seems to be underestimated. One of the most consistent findings observed in ASD patients is loss of Purkinje cells (PCs). Such a defect may be caused by dysregulation of glutamate homeostasis, which is maintained mainly by BG. Moreover, these glial cells are involved in long-term depression (LTD), a form of plasticity which can additionally subserve neuroprotective functions. The aim of presented review is to summarize the current knowledge about interactions which occur between PC and BG, with special emphasis on those which are relevant to the survival and proper functioning of cerebellar neurons.

Aim: Without taking into consideration the pedagogical justification for doing the strength training by prisoners, the authors of this study discuss the problem of the consequences of allowing prisoners to do the strength training freely. The study was conducted to determine the frequency and the location of the overload changes in the musculoskeletal system of prisoners who do the strength training as well as the presumable reasons for such changes. Methods: The study was conducted with the use of an interview technique among 44 men, repeat offenders serving a sentence of imprisonment in a prison in Inowrocław, regularly engaged in strength training in their free time. Results: The respondents trained quite often (more than 5 times a week), slightly more than a half of them started the training with the warm up, and 64% did not do any stretching exercises after the training. The overload changes associated with strength training affected 30% of the respondents. Conclusion: The high level of injury among prisoners who do the strength training is due to: too many sessions a week, the lack of warm up and stretching exercises, as well as the insufficient level of knowledge on the prevention from sports injuries.

There is a strong medical demand to search for novel, more efficacious and safer than available, analgesics for the treatment of neuropathic pain. This study investigated antinociceptive activity of intraperitoneally administered 3-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one (LPP1) and pregabalin in the chronic constriction injury (CCI) model of neuropathic pain in mice and evaluated these drugs' influence on motor coordination. In addition, microscopic examinations of the sciatic nerve were performed to assess, if a surgical method or drug treatment caused changes in the structure of this nerve. Moreover, the alterations of nerve growth factor (NGF) content after drug treatment were assessed.Antiallodynic and antihyperalgesic activities of LPP1 and pregabalin were assessed in the von Frey and hot plate tests. Motor-impairing properties were evaluated in the rotarod test. Microscopic examinations of the sciatic nerve were performed using electron microscope. In immunohistochemical assays the content of NGF in the sciatic nerve after single or repeated administration of test drugs was assessed.Microscopic examinations of the sciatic nerve revealed ultrastructural changes in nerve fibers indicating for neurodegenerative processes induced by CCI. Seven days after CCI surgery LPP1 and pregabalin reduced tactile allodynia in von Frey test (ED50 values were 1.5 and 15.4 mg/kg, respectively). None of the test drugs at dose range 0.5-100 mg/kg induced motor deficits in the rotarod test. In immunohistochemical assays repeated doses of pregabalin and LPP1 elevated NGF content.LPP1 has antiallodynic properties and is an interesting lead structure in the search for novel analgesics used in neuropathic pain.

The paper reports five species of Aciculidae from calcareous intercalations within lignite units of the opencast brown coal mine in Belchatów. Two of them, Acicula schlickumi (Schütt 1967) and Renea pretiosa (Andreae 1904) were only poorly known on the basis of some incomplete shells, while Acicula crassistoma is described as a new species.

Various deconvolution algorithms are often used for restoration of digital images. Image deconvolution is especially needed for the correction of three-dimensional images obtained by confocal laser scanning microscopy. Such images suffer from distortions, particularly in the Z dimension. As a result, reliable automatic segmentation of these images may be difficult or even impossible. Effective deconvolution algorithms are memory-intensive and time-consuming. In this work, we propose a parallel version of the well-known Richardson-Lucy deconvolution algorithm developed for a system with distributed memory and implemented with the use of Message Passing Interface (MPI). It enables significantly more rapid deconvolution of two-dimensional and three- dimensional images by efficiently splitting the computation across multiple computers. The implementation of this algorithm can be used on professional clusters provided by computing centers as well as on simple networks of ordinary PC machines. Microsc. Res. Tech. 00:000-000, 2009. V C 2009 Wiley-Liss, Inc.

Recent discoveries suggest that astrocytes are an integral part of synaptic connections, as they sense and modulate synaptic activity. Moreover, there is evidence that astrocytes change the number of synaptic connections directly via synaptogenic signals or indirectly, by modifying the morphology of axons and dendrites. Here, we formulate the hypothesis that astrocytes mediate the morphological homeostasis of nerve cells, which is any adaptation of the morphology of a neuron to preserve its ability to respond to and generate synaptic activity during learning and mernory-induced changes. We argue that astrocytes control neuronal morphology locally and across long-ranging assemblies of neurons and that on the other hand, astrocytes, are part of the engram with plasticity-related changes affecting their morphology.

Transient global ischemia induces intensive neuronal degeneration in the hippocampal CA1 pyramidal layer, accompanied by reactive transformation of glial cells. Previously, we have shown using the double immunostaining method that the NGF receptors (NGFR) p75 and TrkA are expressed mainly on subpopulations of GFAP+ astrocytes, and this expression increases progressively after ischemia. In the presented study, we analyzed quantitatively the morphological transformations of cells immunopositive for GFAP or NGF receptors in the stratum radiatum of the CA1 hippocampal area in different survival periods after ischemia, evoked by 10-min cardiac arrest in adult rats. In control brains, NGF receptors were expressed only on small cells with poorly ramified processes. After ischemia, the NGFR+ cells increased in size and morphological complexity (measured using fractal analysis). However, even 2 weeks after ischemia these cells did not reach the size and value of the fractal dimension typical of the largest GFAP+ astrocytes. Moreover, the reaction of NGFR+ cells was significantly delayed in comparison with the total astrocyte population. The obtained results suggest that NGF receptors are expressed mainly by immature astrocytes and ischemia induces the maturation of these cells.

Morphological transformation of lectin-positive microglia/macrophages in the developing rat cerebral hemisphere was analysed using quantitative methods. During the first postnatal month, the cells showed increases in their size and fractal dimension accompanied by a simultaneous decrease in their solidity. Regional variations in dynamics of the process indicated the existence of spatio-temporal developmental gradients within the cerebral hemisphere wall which might correspond with regional patterns of neuronal differentiation. Results of the present study prove that the quantitative methods can be the source of reliable data replacing subjective cell typologies.

The present study focuses on application of quantitative methods measuring differences between particular morphological types of microglial cells as well as between their proliferating and non-proliferating examples. On the basis of subjective classification, microglial cells of three morphological types (ramified, hypertrophied and bushy) were selected from the neocortex of injured rat brain. Thereafter, the morphological complexity of each cell was assessed by calculation its fractal dimension as well as its form factor, convexity, ramification factor and solidity. The fractal dimension seemed a good parameter for detecting small changes in the space-filing capacity of cells, for example, it shows differences between ramified cells from control and injured brains. This measure seemed insensitive to some aspects of cell morphology. To obtain precise quantification of observed changes other morphological parameters had to be applied. Proliferating and non-proliferating microglial cells displayed significant differences in their solidity and ramification factors, but not in fractal dimension and convexity. The results indicated that proliferating microglia were more massive and less-ramified but they did not reduce their spatial complexity.

Pregnant Wistar rats were exposed to a single 1.0 Gy dose of gamma-irradiation on gestational day 13, 15, 17 or 19. Thirty-day-old male offspring received a mechanical lesion in the left cerebral hemisphere. One, 2 or 4 days after the injury the rats were injected with [3H]thymidine and sacrificed 4 h after the injection. Thereafter, brain sections were immunostained for GFAP or S100 beta protein, subjected to autoradiography and examined microscopically to record immunopositive astrocytes labelled with [3H]thymidine. Statistically significant elevation of the reactive astrocyte proliferation was revealed on the 2nd day following injury in brains irradiated on gestational day 15. The results represent the first in vivo evidence that a low-dose prenatal gamma-irradiation can induce a long-term increase in the ability of astroglia to proliferate in response to injury.

The distribution of monoamine transmitters in the area near the ventral surface of the rat medulla oblongata was studied using the Falck-Hillarp histofluorescence method. Histological examination and scanning electron microscopy of these regions were also performed. It was found that there is a wide area dense with catecholamine terminals in the external layer of the ventral medulla oblongata. 5-Hydroxytryptamine-containing terminals and nerve cell bodies on and near the surface were also found. Due to their superficial localization these monoamines may influence the content of cerebrospinal fluid and in this way have effects on cardiovascular and other physiological functions.

Treelike structures are very common in nature. They are defined as structures which bifurcate but do not form any cycles. Apart from trees examples of such structure are neurons, snow flakes, river deltas, bronchial trees, corals, cardiovascular systems and many more. One of the aims of mathematical modeling of the natural systems is establishment of effective description and generation methods of treelike structures. In the midst of such methods Diffusion Limited Aggregation, L-systems as well as heuristics dedicated to certain issues produce desired results. A great deal of treelike structures reveals self-similarity features that indicates possibility of fractal geometry utilization in order to their description. In a number of cases treelike structure generalization method is based on a recurrent algorithm. Structures generated according to this approach usually show fractal features, therefore it leads to question if living systems are generated recurrently. Concerning living systems relatively inconsiderable amount of genetic information gives rise to highly sophisticated structures creation. It could be suspected that recurrent mechanisms are crucial in the growth process of complex organic structures.

Following a mechanical lesion of the left cerebral hemisphere, newborn male rats received a single injection of recombinant rat interferon gamma (IFN gamma) into the lesion cavity at doses of 5, 50 and 500 U. One or two days after the injury the rats were injected with H-3-thymidine. Brain sections were immunostained for glial fibrillary acidic protein (GFAP), subjected to autoradiography and examined microscopically to record proliferating GFAP-immunopositive (GFAP+) astrocytes labeled with H-3-thymidine. Following the intermediate 50 U dose of IFN gamma, numbers of GFAP+ astrocytes and of their mitoses on day 1 after injury were significantly higher than in controls. Nevertheless, the astrocyte labeling index remained at the control level. Injections of the minimal 5 U or the maximal 500 U doses of IFN gamma had no effect on that day. On day 2, however, each of the three doses evoked a statistically significant but dose-independent reduction of the labeling index without similar changes in total number of GFAP+ astrocytes or in numbers of their divisions. The changes appear to indicate a non-linear relation between the intensity of reactive behaviour of astrocytes and the amount of IFN gamma injected into the lesion area. On the basis of previous publications, IFN gamma effects on the astrocyte reactivity are discussed as being age-dependent.