Innovation in the treatment of non-melanoma skin cancer: daylight photodynamic therapy / Új eljárás a nem melanoma típusú bordaganatok kezelésében: "daylight" fotodinámiás terápia

Introduction: Photodynamic therapy is indicated for the treatment of superficial basal cell carcinoma, Bowen's disease and actinic keratosis. Reactive oxygen radicals are released from the metabolite of the topically applied photosensitizer that is excited by light, which selectively leads to the destruction of tumor cells. The procedure can be performed with an artificial light source or with the use of sunlight. The latter is called daylight photodynamic therapy, which is an effective and painless procedure. Objective: Our aim was to introduce daylight photodynamic therapy in actinic keratoses at our department and to optimize the treatment protocol for the local climatic conditions. Method: Three clinical trials were performed. The difference between the treatment protocols was between the incubation time of the photosensitizer on the skin and in the time patients spent under the sunlight. Results: When using the international treatment protocol, 73% of the actinic keratoses showed complete, while 27% partial remission. By reducing the proportion of time patients spent outdoor, complete remission was achieved in

Lesion-induced changes of brevican expression in the perineuronal net of the superior vestibular nucleus.

Damage to the vestibular sense organs evokes static and dynamic deficits in the eye movements, posture and vegetative functions. After a shorter or longer period of time, the vestibular function is partially or completely restored via a series of processes such as modification in the efficacy of synaptic inputs. As the plasticity of adult central nervous system is associated with the alteration of extracellular matrix, including its condensed form, the perineuronal net, we studied the changes of brevican expression in the perineuronal nets of the superior vestibular nucleus after unilateral labyrinth lesion. Our results demonstrated that the unilateral labyrinth lesion and subsequent compensation are accompanied by the changing of brevican staining pattern in the perineuronal nets of superior vestibular nucleus of the rat. The reduction of brevican in the perineuronal nets of superior vestibular nucleus may contribute to the vestibular plasticity by suspending the non-permissive role of brevican in the restoration of perineuronal net assembly. After a transitory decrease, the brevican expression restored to the control level parallel to the partial restoration of impaired vestibular function. The bilateral changing in the brevican expression supports the involvement of commissural vestibular fibers in the vestibular compensation. All experimental procedures were approved by the 'University of Debrecen - Committee of Animal Welfare' (approval No. 6/2017/DEMAB) and the 'Scientific Ethics Committee of Animal Experimentation' (approval No. HB/06/ÉLB/2270-10/2017; approved on June 6, 2017).

Distribution and classification of the extracellular matrix in the olfactory bulb.

Extracellular matrix (ECM) became an important player over the last few decades when studying the plasticity and regeneration of the central nervous system. In spite of the established role of ECM in these processes throughout the central nervous system (CNS), only few papers were published on the ECM of the olfactory system, which shows a lifelong plasticity, synaptic remodeling and postnatal neurogenesis. In the present study, we have described the localization and organization of major ECM molecules, the hyaluronan, the lecticans, tenascin-R and HAPLN1 link protein in the olfactory bulb (OB) of the rat. We detected all of these molecules in the OB showing differences in the molecular composition, staining intensity, and organization of ECM between the layers and in some cases within a single layer. One of the striking features of ECM staining pattern in the OB was that the reactions are shown dominantly in the neuropil, the PNNs were found rarely and they exhibited thin or diffuse appearance Similar organization was shown in human and mice samples. As the PNN limits the neural plasticity, its rare appearance may be related to the high degree of plasticity in the OB.

Distribution of the Extracellular Matrix in the Pararubral Area of the Rat.

Previously we described similarities and differences in the organization and molecular composition of an aggrecan based extracellular matrix (ECM) in three precerebellar nuclei, the inferior olive, the prepositus hypoglossi nucleus and the red nucleus of the rat associated with their specific cytoarchitecture, connection and function in the vestibular system. The aim of present study is to map the ECM pattern in a mesencephalic precerebellar nucleus, the pararubral area, which has a unique function among the precerebellar nuclei with its retinal connection and involvement in the circadian rhythm regulation. Using histochemistry and immunohistochemistry we have described for the first time the presence of major ECM components, the hyaluronan, aggrecan, versican, neurocan, brevican, tenascin-R (TN-R), and the HAPLN1 link protein in the pararubral area. The most common form of the aggrecan based ECM was the diffuse network in the neuropil, but each type of the condensed forms was also recognizable. Characteristic perineuronal nets (PNNs) were only recognizable with Wisteria floribunda agglutinin (WFA) and aggrecan staining around some of the medium-sized neurons, whereas the small cells were rarely surrounded by a weakly stained PNNs. The moderate expression of key molecules of PNN, the hyaluronan (HA) and HAPLN1 suggests that the lesser stability of ECM assembly around the pararubral neurons may allow quicker response to the modified neuronal activity and contributes to the high level of plasticity in the vestibular system.

Comparing the effects of excess copper in the leaves of Brassica juncea (L. Czern) and Brassica napus (L.) seedlings: Growth inhibition, oxidative stress and photosynthetic damage.

Hydroponic experiments were conducted to compare the effects of excess copper (Cu) on growth and photosynthesis in young Indian mustard (Brassica juncea) and oilseed rape (Brassica napus). We compared the effects of excess Cu on the two Brassica species at different physiological levels from antioxidant levels to photosynthetic activity. Nine-day-old plants were treated with Cu (10, 25 and 50 µM CuSO4) for 7 and 14 days. Both species took up Cu from the external solution to a similar degree but showed slight root-to-shoot translocation. Furthermore, after seven days of treatment, excess Cu significantly decreased other microelement content, such as iron (Fe) and manganese (Mn), especially in the shoots of B. napus. As a consequence, the leaves of young Brassica napus plants showed decreased concentrations of photosynthetic pigments and more intense growth inhibition; however, accumulation of highly reactive oxygen species (hROS) were not detected. After 14 days of Cu exposure the reduction of Fe and Mn contents and shoot growth proved to be comparable in the two species. Moreover, a significant Cu-induced hROS accumulation was observed in both Brassica species. The diminution in pigment contents and photosynthetic efficiency were more pronounced in B. napus during prolonged Cu exposure. Based on all the parameters, B. juncea appears to be more resistant to excess Cu than B. napus, rendering it a species with higher potential for phytoremediation.

Molecular composition and expression pattern of the extracellular matrix in a mossy fiber-generating precerebellar nucleus of rat, the prepositus hypoglossi.

The prepositus hypoglossi nucleus (PHN) is a mossy fiber-generating precerebellar nucleus of the brainstem, regarded as one of the neural integrators of the vestibulo-ocular reflex. The aim of the present work is to reveal the distribution of various molecular components of the extracellular matrix (ECM) in the prepositus hypoglossi nucleus by using histochemical and immunohistochemical methods. Our most characteristic finding was the accumulation of the ECM as perineuronal net (PNN) and axonal coat and we detected conspicuous differences between the magnocellular (PHNm) and parvocellular (PHNp) divisions of the PHN. PNNs were well developed in the PHNm, whereas the pericellular positivity was almost absent in the PHNp, here a diffuse ECM was observed. In the PHNm the perineuronal net explored the most intense staining with the aggrecan, and tenascin-R antibodies followed by the hyaluronan, then least with reactions for chondroitin sulfate-based proteoglycan components and HAPLN1 link protein reactions, but PNNs were not observed with the versican, neurocan, and brevican staining. We hypothesized that the difference in the ECM organization of the two subnuclei is associated with their different connections, cytoarchitecture, physiological properties and with their different functions in the vestibular system.

Brainstem circuits underlying the prey-catching behavior of the frog.

Prey-catching behavior (PCB) of the frog consists of a sequence of movements as a stimulus-response chain of the behavioral pattern in which each action presents a signal for the subsequent event. The transformation of visual information into appropriate spatiotemporal patterns of motor activity is carried out by the motor pattern generators located in the brainstem reticular formation. The motor pattern generators provide input to the motoneurons either directly or via the last-order premotor interneurons (LOPI). Although the feeding program is predetermined in this way, various sensory mechanisms control the motor activity. By using neuronal labeling methods, we have studied the morphological details of sensorimotor integration related to the hypoglossal motoneurons to provide further insight into the neuronal circuits underlying the PCB in ranid frogs. Our major findings are as follows. (1) Dendrodendritic and dendrosomatic contacts established by the crossing dendrites of hypoglossal (XII) motoneurons may serve as a morphological option for co-activation, synchronization and proper timing of the bilateral activity of tongue muscles. The crossing dendrites may also provide a feedforward amplification of various signals to the XII motoneurons. The overlapping dendritic territories of the motoneurons innervating protractor and retractor muscles may facilitate the coordinated activities of the agonistic and antagonistic muscles. (2) The musculotopic organization of the XII motoneurons is reflected in the distribution of LOPI for the protractor and retractor muscles of the tongue. (3) Direct sensory inputs from the trigeminal, vestibular, glossopharyngeal-vagal, hypoglossal and spinal afferent fibers to the XII motoneurons may modulate the basic motor pattern and contribute to the plasticity of neuronal circuits. (4) The electrical couplings observed in the vestibulocerebellar neuronal circuits may synchronize and amplify the afferent signals. The combination of chemical and electrical impulse transmission provides a mechanism by which motoneurons can be activated sequentially.

Molecular composition of extracellular matrix in the vestibular nuclei of the rat.

Previous studies have demonstrated that the molecular and structural composition of the extracellular matrix (ECM) shows regional differences in the central nervous system. By using histochemical and immunohistochemical methods, we provide here a detailed map of the distribution of ECM molecules in the vestibular nuclear complex (VNC) of the rat. We have observed common characteristics of the ECM staining pattern in the VNC and a number of differences among the individual vestibular nuclei and their subdivisions. The perineuronal net (PNN), which is the pericellular condensation of ECM, showed the most intense staining for hyaluronan, aggrecan, brevican and tenascin-R in the superior, lateral and medial vestibular nuclei, whereas the HAPLN1 link protein and the neurocan exhibited moderate staining intensity. The rostral part of the descending vestibular nucleus (DVN) presented a similar staining pattern in the PNN, with the exception of brevican, which was negative. The caudal part of the DVN had the weakest staining for all ECM molecules in the PNN. Throughout the VNC, versican staining in the PNN, when present, was distinctive due to its punctuate appearance. The neuropil also exhibited heterogeneity among the individual vestibular nuclei in ECM staining pattern and intensity. We find that the heterogeneous distribution of ECM molecules is associated in many cases with the variable cytoarchitecture and hodological organization of the vestibular nuclei, and propose that differences in the ECM composition may be related to specific neuronal functions associated with gaze and posture control and vestibular compensation.

Effect of unilateral labyrinthectomy on the molecular composition of perineuronal nets in the lateral vestibular nucleus of the rat.

Disturbances in vestibular functions caused by unilateral labyrinthectomy (UL) are spontaneously restored during the process of vestibular compensation due to the plasticity of CNS. The underlying molecular background of vestibular compensation is not yet fully understood. Recent studies have shown that the extracellular matrix (ECM) molecules have either permissive or non-permissive effect on the neural plasticity. In our previous study we have demonstrated changes in the expression of hyaluronan (HA) in the vestibular nuclei (VN) of the frog following peripheral vestibular lesion. The present work was undertaken to examine the expression of the HA and chondroitin sulfate proteoglycans (CSPGs) in the lateral vestibular nucleus (LVN) of the rat following UL by using histochemical methods. On the first postoperative day, the condensation of the ECM around the neurons, the perineuronal net (PNN) was not distinguished from the surrounding neuropil on the side of UL indicating the desorganization of its molecular structure. At survival day 3, the PNN was recognizable with the HA probe, whereas its staining for the CSPGs was restored by the time of the seventh postoperative day. In the neuropil, the intensity of the HA increased on the operated side, while the CSPGs reaction almost completely disappeared. The present study have demonstrated for the first time that the UL is accompanied by the modification of the HA, and CSPG staining pattern in the PNN of the LVN in the rat. As the reorganization of the PNN corresponds to the restoration of spontaneous activity of vestibular neurons, our study implies the role of HA and CSPGs in the vestibular compensation.

Comment on "tests of scaling and universality of the distributions of trade size and share volume: evidence from three distinct markets".

In a recent publication, Plerou and Stanley [Phys. Rev. E 76, 046109 (2007)] use the Meerschaert-Scheffler estimator to verify the "inverse half-cubic law" of trade size distributions. We show that this procedure systematically underestimates these tail exponents.

[The prevalence of melanocytic naevi among teenagers]. / A festéksejtes anyajegyek elofordulása tinédzsereken.

UNLABELLED: Malignant melanoma is an increasing public health problem worldwide; accordingly, identification of the constitutional and environmental factors which contribute to the development of the disease, and hence identification of the individuals at high risk of melanoma, are indispensable steps in all primary prevention efforts. AIM: The objective of the present study was to assess the prevalence of different pigmented lesions among schoolchildren, and to investigate their relationship with phenotypic pigmentary characteristics, sun exposure and other factors. METHODS: A cross-sectional study was performed in two secondary schools in Szeged, Hungary. A total of 1320 schoolchildren, aged 14 to 18 years, underwent a whole-body skin examination. A standardized questionnaire was used to collect data on phenotypic, sun exposure and other variables. RESULTS: Between 1-10 common melanocytic naevi were found in 27% of the participants, and naevi numbers were in the range between 10-100 in 67%. 5.4% of them had more than 100 common melanocytic naevi. The prevalence of clinically atypical naevi was 24.3%. Congenital naevi were detected in 6.2% of the schoolchildren. A statistically significant association was found between the number of pigmented lesions and gender, hair colour, eye colour, skin phototype, the history of severe painful sunburns, and the family history of a large number of melanocytic naevi. CONCLUSIONS: Our study population displayed a markedly high prevalence of clinically atypical melanocytic naevi. Moreover, a considerable proportion of the investigated individuals had multiple common melanocytic naevi. Since the presence of large number of melanocytic naevi is a strong predictor for future melanoma development, health educational programmes on melanoma prevention should be aimed at young age groups.

On sensitivity amplification in intracellular signaling cascades.

Sensitivity amplification has long been regarded as a virtually universal property of signal transduction cascades, yet a comprehensive parameter analysis remains a challenge even for relatively simple networks. We use a fast and accurate method to compute properties of multilevel cascades of activation-inactivation cycles and show that the monocyclic cascades amplify sensitivity only under specific conditions. In particular, it is found that efficient sensitivity amplification in a cascade, relative to the sensitivities of individual cycles, requires asymmetry in saturation of converter enzymes, with inhibitors much more saturated than activators.

Vestibulotrigeminal pathways in the frog, Rana esculenta.

The aim of this study was to investigate whether primary vestibular afferent fibers establish direct connections with the motor and sensory trigeminal system in the brainstem of the frog. The experiments were carried out on Rana esculenta. In anaesthetized animals the trigeminal and vestibular nerves were prepared, and their proximal stumps were labeled either with fluorescein binding dextran amine (trigeminal nerve) or tetramethylrhodamine dextran amine (vestibulocochlear nerve). With a confocal laser scanning microscope we could detect close connections between the vestibular fibers and branches of the dorsal dendritic array of the jaw-closing motoneurons, suggestive of monosynaptic contacts. In the other parts of the brainstem, vestibular terminals were detected in the termination areas of the mesencephalic trigeminal nucleus and of the Gasserian (Vth) ganglion and they were probably involved in polysynaptic connections. In agreement with the results obtained in mammalian species, the present findings suggest that the vestibulotrigeminal relationship is quite complex and uses multiple pathways to connect the vestibular apparatus with the motor and sensory nuclei of the trigeminal nerve in the anurans as well.

Dendrodendritic and dendrosomatic contacts between oculomotor and trochlear motoneurons of the frog, Rana esculenta.

Gaze fixation requires very fast movements of the eye during body displacement. The morphological and physiological background of the very fine and continuous tuning of gaze fixation is not yet fully understood. In a previous study we have shown that the dendrites of oculomotor neurons form bundles which invade the trochlear nucleus, and vice versa, trochlear dendritic bundles invade the oculomotor nucleus. Earlier physiological observations demonstrating electrotonic coupling between dendrites of spinal motoneurons in the frog suggest a similar mechanism between the oculomotor and trochlear motoneurons. We studied a possible morphological basis of gaze fixation. The experiments were carried out on common water frogs, Rana esculenta. The trochlear and oculomotor nerves were cut, and their proximal stumps were labeled simultaneously with different retrograde fluorescent tracers. Using confocal laser scanning microscope we detected a large number of close contacts in both nuclei, the majority of them were dendrodendritic apposition. The distance between the adjacent profiles suggested close membrane appositions without intercalating glial or neuronal elements. At the ultrastructural level, the dendrodendritic and dendrosomatic contacts did not show any morphological specialization; the long membrane appositions may provide ephaptic interactions between the neighboring profiles. This electrotonic coupling between the oculomotor and trochlear nerve motoneurons may promote the co-activation of the muscles responsible for vertical eye movements.

Organization of last-order premotor interneurons related to the protraction of tongue in the frog, Rana esculenta.

Moving visual stimuli elicit a sequence of coordinated activity of muscles including tongue protraction. Morphological and physiological studies fail to reveal any direct tectal projections to hypoglossal motoneurons suggesting that the last-order premotor interneurons (LOPI) are the direct recipients of neural activities generated in the optic tectum. The aim of this study is to analyze the topographical organization of the last-order premotor interneurons related to protractor muscles of the tongue. In Rana esculenta, biotinylated dextran amine (BDA) was injected by iontophoresis into the subnucleus of the hypoglossal nerve containing the motoneurons of protractor muscles of the tongue. For visualizing BDA, sections were treated with avidin-biotin complex and a nickel-enhanced DAB chromogen reaction. The position of labeled neurons was reconstructed with a Neurolucida equipment. Morphologically heterogeneous populations of neurons were detected bilaterally, the majority of them were distributed ipsilateral to the site of injection and extended 1200 microm in rostral and 500 microm in caudal directions. Labeled neurons were found in the rhombencephalic reticular formation, the vestibular nuclei, the nucleus prepositus hypoglossi, the nucleus of solitary tract, the spinal nucleus of trigeminal nerve and the dorsal column nuclei. Our results indicate that the majority of last-order premotor interneurons related to protractor muscles of the tongue are located in the reticular formation of the brainstem. Since this area also receives a significant input from the vestibular system and from proprioceptive fibers, the last-order premotor interneurons presented here may be the target of convergence of sensory modalities involved in prey-catching behavior.

Organization of dye-coupled cerebellar granule cells labeled from afferent vestibular and dorsal root fibers in the frog Rana esculenta.

Application of neurobiotin to the nerves of individual labyrinthine organs and dorsal root fibers of limb-innervating segments of the frog resulted in labeling of granule cells in the cerebellum showing a significant overlap with a partial segregation in the related areas of termination. In different parts of the cerebellum, various combinations of different canal and otolith organ-related granule cells have been discerned. The difference in the extension of territories of vertical canals vs. horizontal canals may reflect their different involvement in the vestibuloocular and vestibulospinal reflex. Dye-coupled cells related to the lagenar and saccular neurons were localized in more rostral parts of the cerebellum, whereas cells of the utricle were represented only in its caudal half. This separation is supportive of the dual function of the lagena and the saccule. The territories of granule cells related to the cervical and lumbar segments of the spinal cord were almost completely separated along the rostrocaudal axis of cerebellum, whereas their territories were almost entirely overlapping in the mediolateral and ventrodorsal directions. The partial overlap of labyrinthine organ-related and dorsal root fiber-related granule cells are suggestive of a convergence of sensory modalities involved in the sense of balance. We propose that the afferent input of vestibular and proprioceptive fibers mediated by gap junctions to the cerebellar granule cells subserve one of the possible morphological correlates of a very rapid modification of the motor activity in the vestibulocerebellospinal neuronal circuit.