Editorial: frontiers in the pharmacological manipulation of intracellular cAMP levels

No abstract available

Development and assessment of in vitro simulation approaches to intracerebral haemorrhage

This current PhD Thesis in Neuropathology focuses on the development and assessment of in vitro simulation approaches to intracerebral haemorrhage. The PhD Thesis provides a clinical and experimental neuropathological overview of intracerebral haemorrhage as well as an account of the in vitro simulation approaches to the disease, before proceeding to the presentation of the experimental work designed and performed by the author. The development of the herein presented in vitro simulation approaches to intracerebral haemorrhage was based on the use of an immortalized embryonic murine hippocampal cell-line (mHippoE-14) and its response to oligomycin-A and ferrum or haemin under appropriately selected conditions (aiming to simulate the natural history of the disease in a more reliable manner). The PhD Thesis provides a characterization of the mHippoE-14 cell-line (through a real-time cellular response analysis and a cytomorphological characterization), before proceeding to the actual experimental justification of the conditions chosen for the development of the herein presented in vitro simulation approaches to intracerebral haemorrhage, and their assessment. The latter was performed through the undertaking of: (a) real-time cellular response analysis, (b) cytomorphological assessment, (c) profiling of neuronal markers’ expression, (d) neurochemical assessment, and (e) proteomic profiling. All experiments were performed at the University of Glasgow. The current PhD Thesis also provides a critical appraisal of: (a) the utility, novelty and limitations of the developed in vitro simulation approaches, and (b) the positioning of the developed in vitro simulation approaches within the neuropathopoietic context

Non-genetic therapeutic approaches to Canavan disease

Canavan disease (CD) is a rare leukodystrophy characterized by diffuse spongiform white matter degeneration, dysmyelination and intramyelinic oedema with consequent impairment of psychomotor development and early death. The molecular cause of CD has been identified as being mutations of the gene encoding the enzyme aspartoacylase (ASPA) leading to its functional deficiency. The physiological role of ASPA is to hydrolyse N-acetyl-l-aspartic acid (NAA), producing l-aspartic acid and acetate; as a result, its deficiency leads to abnormally high central nervous system NAA levels. The aim of this article is to review what is currently known regarding the aetiopathogenesis and treatment of CD, with emphasis on the non-genetic therapeutic strategies, both at an experimental and a clinical level, by highlighting: (a) major related hypotheses, (b) the results of the available experimental simulatory approaches, as well as (c) the relevance of the so far examined markers of CD neuropathology. The potential and the limitations of the current non-genetic neuroprotective approaches to the treatment of CD are particularly discussed in the current article, in a context that could be used to direct future experimental and (eventually) clinical work in the field

Формирование творческой речевой активности дошкольников с функциональными нарушениями зрения

Рассматриваются основные этапы формирования навыков творческого рассказывания у дошкольников с функциональными нарушениями зрения, перечисляются эффективные приемы стимулирования творческой речевой активности дошкольников с ослабленным зрение

Coxsackievirus and adenovirus receptor expression in human endometrial adenocarcinoma: possible clinical implications

The coxsackievirus and adenovirus receptor (CAR) is a crucial receptor for the entry of both coxsackie B viruses and adenoviruses into host cells. CAR expression on tumor cells was reported to be associated with their sensitivity to adenoviral infection, while it was considered as a surrogate marker for monitoring and/or predicting the outcome of adenovirus-mediated gene therapy. The aim of the present study was to evaluate the clinical significance of CAR expression in endometrial adenocarcinoma. CAR expression was assessed immunohistochemically in tumoral samples of 41 endometrial adenocarcinoma patients and was statistically analyzed in relation to various clinicopathological parameters, tumor proliferative capacity and patient survival. CAR positivity was noted in 23 out of 41 (56%) endometrial adenocarcinoma cases, while high CAR expression in 8 out of 23 (35%) positive ones. CAR intensity of immunostaining was classified as mild in 11 (48%), moderate in 10 (43%) and intense in 2 (9%) out of the 23 positive cases. CAR positivity was significantly associated with tumor histological grade (p = 0.036), as well differentiated tumors more frequently demonstrating no CAR expression. CAR staining intensity was significantly associated with tumor histological type (p = 0.016), as tumors possessing squamous elements presented more frequently intense CAR immunostaining. High CAR expression showed a trend to be correlated with increased tumor proliferative capacity (p = 0.057). Patients with tumors presenting moderate or intense CAR staining intensity were characterized by longer survival times than those with mild one; however, this difference did not reach statistical significance. These data reveal, for the first time, the expression of CAR in clinical material obtained from patients with endometrial adenocarcinoma in relation to important clinicopathological parameters for their management. As CAR appears to modulate the proliferation and characteristics of cancer cells, its expression could be considered of possible clinical importance for future (gene) therapy applications

A short commentary on Aristotle's scientific legacy and his definition of the physiologist

The roots of physiology - on the basis of a systematic study of the human body's functions and their correlation to anatomy - date back to the works of Aristotle. The pupil of Plato and the tutor of Alexander the Great was a one-man university, and his contributions to the medical sciences have been immense. His surviving works highlight the first serious approach towards the rejection of metaphysical and mythological thought, and have: (i) demonstrated a deep appreciation for a systematic, non-metaphysical study of the natural world, (ii) set the foundations of comparative and human anatomy, (iii) established the first (indirect) definition of the "physiologist", and (iv) exercised a dominant influence upon the subsequent history of Hellenistic, European and Arabic Medicine. The current letter provides a short commentary on the historical account of Physiology as a scientific field and underlines the unique legacy that Aristotle has provided us with

Prerequisites for a reliable introduction of in vitro neurotoxicity testing within the REACH framework

No abstract available

Contribution to the study of experimentally-simulated toxic and metabolic encephalopathies

This current PhD Thesis (by published work / retrospective) in Neuroscience focuses on performed studies of three crucial brain enzyme activities under seven categories of experimentally- simulated toxic and metabolic encephalopathies. The studied enzymes were: (a) acetylcholinesterase (AChE, EC 3.1.1.7), (b) sodium-potassium adenosine triphosphatase (Na+,K+- ATPase, EC 3.6.3.9, formerly EC 3.6.1.3), and (c) magnesium adenosine triphosphatase (Mg2+- ATPase, EC 3.6.3.2, formerly EC 3.6.1.3). The studied experimentally-simulated toxic and metabolic encephalopathies were: (a) thyroid-hormone-related brain dysfunctions (as a result of hyper- or hypothyroidism), (b) thioacetamide-induced fulminant hepatic encephalopathy, (c) streptozotocin-induced diabetic encephalopathy, (d) experimentally-simulated Wernicke’s encephalopathy (arising from chronic ethanol consumption, dietary thiaminedeprivation and pyrithiamine-administration), (e) manganese-induced neurotoxicity, (f) lanthanum- induced neurotoxicity, and (g) nickel-induced neurotoxicity. Enzymatic activities were determined spectrophotometrically on albino Wistar rat brain homogenates. Assessments of brain homogenates’ antioxidant status, in vivo antioxidant administrations, in vitro experiments, brain homogenates’ enzymatic activity determinations, as well as pure enzyme activity determinations (under various conditions), were performed (wherever required) in order to elucidate the nature of some of the observed in vivo findings, to evaluate the potential limitations of the experimental-simulation techniques and / or to study the potential use of known antioxidants as neuroprotective agents. All experiments were performed at the Medical School of the National and Kapodistrian University of Athens. The current PhD Thesis condenses and presents the significance of the aforementioned contribution to the study of experimentally-simulated toxic and metabolic encephalopathies, based on published work

A short commentary on Aristotle’s scientific legacy and his definition of the physiologist

The roots of physiology — on the basis of a systematic study of the human body’s functions and their correlation to anatomy — date back to the works of Aristotle. The pupil of Plato and the tutor of Alexander the Great was a one-man university, and his contributions to the medical sciences have been immense. His surviving works highlight the first serious approach towards the rejection of metaphysical and mythological thought, and have: (i) demonstrated a deep appreciation for a systematic, non-metaphysical study of the natural world, (ii) set the foundations of comparative and human anatomy, (iii) established the first (indirect) definition of the “physiologist”, and (iv) exercised a dominant influence upon the subsequent history of Hellenistic, European and Arabic Medicine. The current letter provides a short commentary on the historical account of Physiology as a scientific field and underlines the unique legacy that Aristotle has provided us with