Peculiarities of angiogenesis in testicular embryonal carcinoma

Despite the relatively low incidence of testicular germ cell tumors (TGCT), which amount only 1% of all cancers in men worldwide in the epidemiological aspect, unlike tumors of other localizations, it does not become more frequent with age, but reaches its peak in young men of working age what attaches to the problem not only great medical, but also social significance.Estimation of angiogenesis in the tumor is considered as one of the markers for predicting the course of disease, presence of metastases and sensitivity to antitumor antiangiogenic therapy. At the same time, data concerning the study of the mechanisms of blood vessels formation, the work out of methods for estimation of tumorous angiogenesis as well as the use habits of IHC markers of endothelial cells (CD31 and CD34) for assessing the aggressiveness and prognosis of TGCT and, in particular, EC, are absent in the available literature sources.Investigation of peculiarities of neoangiogenesis in the dynamics of testicular embryonal carcinoma progression revealed: significant increasing of relative area of CD31 and CD34 expression as well as vascular density during transition from the initial to the late stages of tumor progression; formation of intratumoral vessels in the embryonal carcinoma occurs by angiogenesis and vasculogenesis with participation of progenitor endothelial cells; embryonal carcinoma is characterized by vasculogenic mimicry in the form of channels formation that do not have endothelial lining

Swelling-Activated Ca2+ Channels Trigger Ca2+ Signals in Merkel Cells

Merkel cell-neurite complexes are highly sensitive touch receptors comprising epidermal Merkel cells and sensory afferents. Based on morphological and molecular studies, Merkel cells are proposed to be mechanosensory cells that signal afferents via neurotransmission; however, functional studies testing this hypothesis in intact skin have produced conflicting results. To test this model in a simplified system, we asked whether purified Merkel cells are directly activated by mechanical stimulation. Cell shape was manipulated with anisotonic solution changes and responses were monitored by Ca2+ imaging with fura-2. We found that hypotonic-induced cell swelling, but not hypertonic solutions, triggered cytoplasmic Ca2+ transients. Several lines of evidence indicate that these signals arise from swelling-activated Ca2+-permeable ion channels. First, transients were reversibly abolished by chelating extracellular Ca2+, demonstrating a requirement for Ca2+ influx across the plasma membrane. Second, Ca2+ transients were initially observed near the plasma membrane in cytoplasmic processes. Third, voltage-activated Ca2+ channel (VACC) antagonists reduced transients by half, suggesting that swelling-activated channels depolarize plasma membranes to activate VACCs. Finally, emptying internal Ca2+ stores attenuated transients by 80%, suggesting Ca2+ release from stores augments swelling-activated Ca2+ signals. To identify candidate mechanotransduction channels, we used RT-PCR to amplify ion-channel transcripts whose pharmacological profiles matched those of hypotonic-evoked Ca2+ signals in Merkel cells. We found 11 amplicons, including PKD1, PKD2, and TRPC1, channels previously implicated in mechanotransduction in other cells. Collectively, these results directly demonstrate that Merkel cells are activated by hypotonic-evoked swelling, identify cellular signaling mechanisms that mediate these responses, and support the hypothesis that Merkel cells contribute to touch reception in the Merkel cell-neurite complex

Merkel Cells as Putative Regulatory Cells in Skin Disorders: An In Vitro Study

Merkel cells (MCs) are involved in mechanoreception, but several lines of evidence suggest that they may also participate in skin disorders through the release of neuropeptides and hormones. In addition, MC hyperplasias have been reported in inflammatory skin diseases. However, neither proliferation nor reactions to the epidermal environment have been demonstrated. We established a culture model enriched in swine MCs to analyze their proliferative capability and to discover MC survival factors and modulators of MC neuroendocrine properties. In culture, MCs reacted to bFGF by extending outgrowths. Conversely, neurotrophins failed to induce cell spreading, suggesting that they do not act as a growth factor for MCs. For the first time, we provide evidence of proliferation in culture through Ki-67 immunoreactivity. We also found that MCs reacted to histamine or activation of the proton gated/osmoreceptor TRPV4 by releasing vasoactive intestinal peptide (VIP). Since VIP is involved in many pathophysiological processes, its release suggests a putative regulatory role for MCs in skin disorders. Moreover, in contrast to mechanotransduction, neuropeptide exocytosis was Ca2+-independent, as inhibition of Ca2+ channels or culture in the absence of Ca2+ failed to decrease the amount of VIP released. We conclude that neuropeptide release and neurotransmitter exocytosis may be two distinct pathways that are differentially regulated

A narrative review on haptic devices: relating the physiology and psychophysical properties of the hand to devices for rehabilitation in central nervous system disorders

Purpose. This paper provides rehabilitation professionals and engineers with a theoretical and pragmatic rationale for the inclusion of haptic feedback in the rehabilitation of central nervous system disorders affecting the hand.Method. A narrative review of haptic devices used in sensorimotor hand rehabilitation was undertaken. Presented papers were selected to outline and clarify the underlying somatosensory mechanisms underpinning these technologies and provide exemplars of the evidence to date.Results. Haptic devices provide kinaesthetic and/or tactile stimulation. Kinaesthetic haptics are beginning to be incorporated in central nervous system rehabilitation, however, there has been limited development of tactile haptics. Clinical research in haptic rehabilitation of the hand is embryonic but initial findings indicate potential clinical benefit. Conclusions. Haptic rehabilitation offers the potential to advance sensorimotor hand rehabilitation but both scientific and pragmatic developments are needed to ensure that its potential is realised.<br/

Loss of Aβ-nerve endings associated with the Merkel cell-neurite complex in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis

The Merkel cell-neurite complex initiates the perception of touch and mediates Aβ slowly adapting type I responses. Lichen planus is a chronic inflammatory autoimmune disease with T-cell-mediated inflammation, whereas hyperkeratosis is characterized with or without epithelial dysplasia in the oral mucosa. To determine the effects of lichen planus and hyperkeratosis on the Merkel cell-neurite complex, healthy oral mucosal epithelium and lesional oral mucosal epithelium of lichen planus and hyperkeratosis patients were stained by immunohistochemistry (the avidin-biotin-peroxidase complex and double immunofluorescence methods) using pan cytokeratin, cytokeratin 20 (K20, a Merkel cell marker), and neurofilament 200 (NF200, a myelinated Aβ- and Aδ-nerve fibre marker) antibodies. NF200-immunoreactive (ir) nerve fibres in healthy tissues and in the lesional oral mucosa epithelium of lichen planus and hyperkeratosis were counted and statistically analysed. In the healthy oral mucosa, K20-positive Merkel cells with and without close association to the intraepithelial NF200-ir nerve fibres were detected. In the lesional oral mucosa of lichen planus and hyperkeratosis patients, extremely rare NF200-ir nerve fibres were detected only in the lamina propria. Compared with healthy tissues, lichen planus and hyperkeratosis tissues had significantly decreased numbers of NF200-ir nerve fibres in the oral mucosal epithelium. Lichen planus and hyperkeratosis were associated with the absence of Aβ-nerve endings in the oral mucosal epithelium. Thus, we conclude that mechanosensation mediated by the Merkel cell-neurite complex in the oral mucosal epithelium is impaired in lichen planus and hyperkeratosis