Activation of melanogenesis by vacuolar type H+-ATPase inhibitors in amelanotic, tyrosinase positive human and mouse melanoma cells

AbstractIn this study, we describe the activation of melanogenesis by selective vacuolar type H+-ATPase inhibitors (bafilomycin A1 and concanamycin A) in amelanotic human and mouse melanoma cells which express tyrosinase but show no melanogenesis. Addition of the inhibitors activated tyrosinase within 4 h, and by 24 h the cells contained measurable amounts of melanin. These effects were not inhibited by cycloheximide (2 μg/ml) which is consistent with a post-translational mechanism of activation. Our findings suggest that melanosomal pH could be an important and dynamic factor in the control of melanogenesis in mammalian cells

Primary culture of avian embryonic heart forming region cells to study the regulation of vertebrate early heart morphogenesis by vitamin A

Copyright: Copyright 2014 Elsevier B.V., All rights reserved.Background: Important knowledge about the role of vitamin A in vertebrate heart development has been obtained using the vitamin A-deficient avian in ovo model which enables the in vivo examination of very early stages of vertebrate heart morphogenesis. These studies have revealed the critical role of the vitamin A-active form, retinoic acid (RA) in the regulation of several developmental genes, including the important growth regulatory factor, transforming growth factor-beta2 (TGFβ2), involved in early events of heart morphogenesis. However, this in ovo model is not readily available for elucidating details of molecular mechanisms determining RA activity, thus limiting further examination of RA-regulated early heart morphogenesis. In order to obtain insights into RA-regulated gene expression during these early events, a reliable in vitro model is needed. Here we describe a cell culture that closely reproduces the in ovo observed regulatory effects of RA on TGFβ2 and on several developmental genes linked to TGFβ signaling during heart morphogenesis. Results: We have developed an avian heart forming region (HFR) cell based in vitro model that displays the characteristics associated with vertebrate early heart morphogenesis, i.e. the expression of Nkx2.5 and GATA4, the cardiogenesis genes, of vascular endothelial growth factor (VEGF-A), the vasculogenesis gene and of fibronectin (FN1), an essential component in building the heart, and the expression of the multifunctional genes TGFβ2 and neogenin (NEO). Importantly, we established that the HFR cell culture is a valid model to study RA-regulated molecular events during heart morphogenesis and that the expression of TGFβ2 as well as the expression of several TGFβ2-linked developmental genes is regulated by RA. Conclusions: Our findings reported here offer a biologically relevant experimental in vitro system for the elucidation of RA-regulated expression of TGFβ2 and other genes involved in vertebrate early cardiovascular morphogenesis.publishersversionPeer reviewe

Oxidative stress parameters in Posttraumatic Stress Disorder risk group patients

Funding Information: The research is supported by European Social Foundation co-financing: Project for Doctoral students support, at Rîga Stradiòð University (No. 2009/0147/1DP/1.1.2.1.2/09/IPIA/ VIAA/009). The views expressed in this article are those of the authors and do not reflect the official policy or position of the Latvian government, Latvian National Armed Forces, Medical Support Centre of Latvian National Armed Forces or any of the institutions with which the authors are affiliated. The authors state no conflict of interest. All authors read and approved the final manuscript.Increased excitotoxity in response to stressors leads to oxidative stress (OS) due to accumulation of excess reactive oxygen/nitrogen species. Neuronal membrane phospholipids are especially susceptible to oxidative damage, which alters signal transduction mechanisms. The Contingent of International Operations (CIO) has been subjected to various extreme stressors that could cause Posttraumatic Stress Disorder (PTSD). Former studies suggest that heterogeneity due to gender, race, age, nutritional condition and variable deployment factors and stressors produce challenges in studying these processes. The research aim was to assess OS levels in the PTSD risk group in CIO. In a prospective study, 143 participants who were Latvian CIO, regular personnel, males, Europeans, average age of 27.4, with the same tasks during the mission, were examined two months before and immediately after a six-month Peace Support Mission (PSM) in Afghanistan. PCL-M questionnaire, valid Latvian language "Military" version was used for PTSD evaluation. Glutathione peroxidase (GPx), superoxide dismutase (SOD) and lipid peroxidation intensity and malondialdehyde (MDA) as OS indicators in blood were determined. Data were processed using SPSS 20.0. The MDA baseline was 2.5582 μM, which after PSM increased by 24.36% (3.1815 μM). The GPx baseline was 8061.98 U/L, which after PSM decreased by 9.35% (7308.31 U/L). The SOD baseline was 1449.20 U/gHB, which after PSM increased by 2.89% (1491.03 U/gHB). The PTSD symptom severity (total PCL-M score) baseline was 22.90 points, which after PSM increased by 14.45% (26.21 points). The PTSD Prevalence rate (PR) baseline was 0.0357, which after PSM increased by 147.06% (0.0882). We conclude that there is positive correlation between increase of OS, PTSD symptoms severity level, and PTSD PR in a group of patients with risk of PTSD - CIO. PTSD PR depends on MDA intensity and OS severity. OS and increased free radical level beyond excitotoxity, is a possible causal factor for clinical manifestation of PTSD.publishersversionPeer reviewe

Intravenous ascorbic acid to prevent and treat cancer-associated sepsis?

The history of ascorbic acid (AA) and cancer has been marked with controversy. Clinical studies evaluating AA in cancer outcome continue to the present day. However, the wealth of data suggesting that AA may be highly beneficial in addressing cancer-associated inflammation, particularly progression to systemic inflammatory response syndrome (SIRS) and multi organ failure (MOF), has been largely overlooked. Patients with advanced cancer are generally deficient in AA. Once these patients develop septic symptoms, a further decrease in ascorbic acid levels occurs. Given the known role of ascorbate in: a) maintaining endothelial and suppression of inflammatory markers; b) protection from sepsis in animal models; and c) direct antineoplastic effects, we propose the use of ascorbate as an adjuvant to existing modalities in the treatment and prevention of cancer-associated sepsis

Regulatory evaluation of Glybera in Europe-two committees, one mission

publishersversionPeer reviewe

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Melanin-concentrating hormone and its receptor are expressed and functional in human skin

In this study, we have demonstrated the presence of melanin-concentrating hormone (MCH) and melanin-concentrating hormone receptor (MCHR1) transcripts in human skin. Sequence analysis confirmed that the transcripts of both genes were identical to those previously found in human brain. In culture, endothelial cells showed pro-MCH expression whereas no signal was found in keratinocytes, melanocytes, and fibroblasts. MCHR1 expression was restricted to melanocytes and melanoma cells. Stimulation of cultured human melanocytes with MCH reduced the α-MSH-induced increase in cAMP production. Furthermore, the melanogenic actions of α-MSH were inhibited by MCH. We propose that the MCH/MCHR1 signalling system is present in human skin and may have a role with the melanocortins in regulating the melanocyte

Precise realtime current consumption measurement in IoT TestBed [version 2; peer review: 1 approved, 2 approved with reservations]

Background The Internet of Things, similar to wireless sensor networks, has been integrated into the daily life of almost everyone. These wearable, stationary, or mobile devices are in multiple locations, collecting data or monitoring and executing certain tasks. Some can monitor environmental values and interact with the environment, while others are used for data collection, entertainment, or even lifesaving. To achieve the wireless part of the system, the majority of sensor nodes are designed to be battery-powered. While battery power has become increasingly ubiquitous, it tends to increase the global carbon footprint of electronic devices. This issue can be mitigated by employing some form of energy harvesting so that batteries can be refilled and the gadget lasts longer, but this does not alter the reality that batteries are still used and eventually discarded. Methods In this paper, the authors emphasize the significance of power consumption in battery-powered devices. To be able to monitor devices’ power consumption, one of the measurable parameters is current. When users know the exact current consumption, they can decrease it by polishing the program or tweaking the duty cycle, making radio transmit fewer data or less frequently, thus decreasing overall power draw. Results In order to simplify current consumption monitoring, the authors have developed a testbed facility that provides real-time current consumption measurements, which may be used to enhance the duty cycle and battery life of the aforementioned devices. Conclusions While minimizing total current consumption is a great way to extend the battery life and, thus, the carbon footprint, the primary culprit in the Internet of Things is radio communications. This transmission is the primary source of current consumption. By determining the exact amount of current drawn during transmission and adjusting it, users can significantly extend battery life