Czynny i bierny transport leków w łożysku ludzkim

The human placenta, characterized by the processes of passive transport and facilitated diffusion, contains numerous active transport proteins, usually located in the microvilli of the syncytiotrophoblast or in the endothelium of the capillaries of the villi. These proteins use either the energy from ATP hydrolysis or other mechanisms resulting, among others, from the formation of the maternofetal ion gradient, which facilitates the transfer of various endogenous substances or xenobiotics across the body membranes. The proteins either trigger the efflux of these substances from the fetal tissues via the placenta into the maternal bloodstream, or conversely, they accumulate them in the fetal tissues. Both the placenta and the fetus are equipped with independent systems of enzymes of 1st and 2nd phase of substrate metabolism, such as CYP450, glucuronyltransferase or sulphatase. An active therapy with a wide range of drugs, often at high toxicity levels, either shortly before or during pregnancy, has naturally posed a question concerning the degree of impermeability of the placental barrier and how effectively it can be crossed, including any possible negative embryotoxic or teratogenic consequences. Such hazards seem to be quite real, as many drugs are substrates for ABC transporters. Also the placenta itself, including its structure, is subject to vast transformations during pregnancy, which may be observed as the thinning of the barrier separating the maternal blood from the fetal one, from 20-30μm in the first trimester of gestation down to 2-4μm in the third trimester of gestation.Streszczenie W łożysku ludzi oprócz transportu biernego oraz dyfuzji ułatwionej zawartych jest wiele aktywnych białek transportowych zazwyczaj zlokalizowanych w mikrokosmkach syncytiotrofoblastu lub w śródbłonkach naczyń włosowatych kosmków. Wykorzystują energię z rozpadu ATP lub inne mechanizmy wynikające między innymi z formułującego się gradientu jonów pomiędzy płodem i matką sprzyjają przenikaniu przez błony różnorodnych substancji endogennych lub ksenobiotyków. Kreują albo ich wyrzut z tkanek płodu przez łożysko do krwi matki lub wręcz przeciwnie kumulują je w jego tkankach. Samo łożysko i płód dysponuje samodzielnymi układami enzymatycznymi pierwszej i drugiej fazy przemian substratów takimi jak: CYP450, glukuronylotransferazy czy sulafatazy. Aktywne postępowanie terapeutyczne z wykorzystaniem szerokiej gamy leków niejednokrotnie o wysokim poziomie toksyczności w okresie przed ciążowym oraz w ciąży rodzi pytanie na ile bariera łożyskowa jest szczelna oraz na ile jest skutecznie pokonywana z możliwymi negatywnymi konsekwencjami o charakterze embriotoksycznym lub teratogennym. Groźba wydaje się być całkowicie realna, bowiem wiele leków to substraty dla transporterów ABC. Również samo łożysko i jego struktura ulega w trakcie ciąży głębokim przewartościowaniom czego miarą może być redukcja dzielącej barierę krew matki od krwi płodu z 20-30μm w pierwszym trymestrze ciąży do 2-4μm w trzecim trymestrze ciąży

Molecular neurochemistry of the lanthanides

Lanthanides, once termed rare‐earth elements, are not as sparce in the environment as their traditional name suggests. Mean litospheric concentrations are in fact comparable to the physiologically fundamental elements such as iodine, cobalt, and selenium. Recent advances in medical technology have resulted in accumulation of lanthanides presenting potential exposure to both our central and peripheral nervous systems. Extensive and detailed studies on these peculiar active metals in the context of their influence on neural functions are therefore urgently required. Almost all neurochemical effects of trivalent lanthanide ions appear to result from the similarity of their radii to the key signaling ion calcium. Lanthanides, especially La3+ and Gd3+ block different types of calcium, potassium, and sodium channels in human and animal neurons, regulate neurotransmitter turnover and release, as well as synaptic activity. Lanthanides also act as modulators of several ionotropic receptors, e.g., GABA, NMDA, and kainate and can also affect numerous signaling mechanisms including NF‐κB and apoptotic‐related endoplasmic reticulum IRE1‐XBP1, PERK, and ATF6 pathways. Several lanthanide ions may cause oxidative neuronal injuries and functional impairment by promoting reactive oxygen species production. However, cerium and yttrium oxides have some unique and promising neuroprotective properties, being able to decrease free radical cell injury and even alleviate motor impairment and cognitive function in animal models of multiple sclerosis and mild traumatic brain damage, respectively. In conclusion, lanthanides affect various neurophysiological processes, altering a large spectrum of brain functions. Thus, a deeper understanding of their potential mechanistic roles during disease and as therapeutic agents requires urgent elucidation

Pharmacomodulation of brain neuromedin U signaling as a potential therapeutic strategy

Neuromedin U (NMU) belongs to a family of multifunctional neuropeptides that modulate the activity of several neural networks of the brain. Acting via metabotropic receptor NMUR2, NMU plays a role in the regulation of multiple systems, including energy homeostasis, stress responses, circadian rhythms, and endocrine signaling. The involvement of NMU signaling in the central regulation of important neurophysiological processes and its disturbances is a potential target for pharmacological modulation. Number of preclinical studies have proven that both modified NMU analogues such as PASR8-NMU or F4R8-NMU and designed NMUR2 agonists, for example, CPN-116, CPN-124 exhibit a distinct pharmacological activity especially when delivered transnasally. Their application can potentially be useful in the more convenient and safe treatment of obesity, eating disorders, Alzheimer's disease-related memory impairment, alcohol addiction, and sleep disturbances. Accumulating findings suggest that pharmacomodulation of the central NMU signaling may be a promising strategy in the treatment of several neuropsychiatric disorders

Mechanics of the Society Mythologen

Połączenie wiedzy z dziedziny medycyny i fizyki kwantowej stworzyło elegancki i spójny model zjawiska świadomości zwany modelem Orch. OR. Zgodnie z tym modelem mózg działa jak żywa maszyna kwantowa, oparta na kompleksach mikrotubul. Zjawiska kwantowe w mikrotubulach umożliwiają doświadczanie qualiów w rzeczywistości Plancka. Qualia mają analogie w innych, omówionych w artykule teoriach współczesnej nauki. Odnoszą się do pól energetycznych — atraktorów, organizujących spostrzeganie, emocje i intelekt. W artykule przedstawiono implikacje społeczne dziedziczenia pól atraktorowych i ich wpływu na świadomość społeczną.The fusion of knowledge from the fields of medicine and quantum physics formed the elegant and consistent model of phenomenon of consciousness, called Orch. OR model. According to this model the brain works as a live quantum machine, based on complexes of microtubules. Quantum phenomena in microtubules allow experiencing qualia in the Planck’s reality. Qualia have analogies in another theories of contemporary science, described in the article. Qualia relate to energetic fields — atractors, which organize the perception, emotions and the intellect. The article presents society implications of inheritance of atractor fields and their influence on society consciousness

Assessment of electrocardiogram interpretation skills among Polish and English Division medical students

Introduction. An electrocardiography (ECG) examination is one of the most frequently performed diagnostic tests. Thecorrect interpretation of ECG, particularly in life-threatening scenarios (LTS) can influence decision-making on appropriateactions and so consequently can have an impact on the life and health of patients. The aim of this study was toevaluate ECG interpretation skills among a study population and to analyse factors determining their score. Material and methods. ECG interpretation skills were assessed using a self-prepared questionnaire including questionsabout demographic data and 20 ECG problems arising from 17 cases. Six of these cases were LTS. Three questionsevaluated basic understanding of heart rhythm, heart rate and axis. The survey was conducted via the internet. Thestudy population consisted of 551 medical, nursing and emergency medicine students. Results. The overall score among Polish medical students was higher than among nursing and emergency medicinestudents. English Division medical students scored almost the same as Polish medical students. Assessed in LTS, theyperformed better than the nursing students, but achieved similar results to those of the emergency medicine students.Analysis of Polish medical students showed that 4th-6th year students scored higher than their younger counterparts.72% of medical students claimed to have self-educated themselves on ECG interpretation. This group had better resultsthan students who had studied ECG only in the classroom. Less than 20% of students from each category of the studypopulation felt that there were enough classes on ECG. Conclusions. The level of ECG interpretative skills noted among medical students is unsatisfactory. Many factors influence ECG knowledge.Wstęp. Badanie elektrokardiograficzne (EKG) jest jednym z najczęściej wykonywanych testów diagnostycznych. Prawidłowa interpretacja zapisu EKG, zwłaszcza w sytuacjach zagrożenia życia, może wpływać na decyzję o wdrożeniu prawidłowego postępowania, a w konsekwencji — na zdrowie i życie pacjentów. Celem badania była ocena umiejętności interpretacji zapisu EKG wśród studentów kierunków medycznych oraz analiza czynników mających wpływ na ich rezultaty. Materiały i metody. Umiejętność interpretacji EKG zbadano za pomocą własnego kwestionariusza zawierającego pytania demograficzne oraz 20 pytań na temat EKG, w tym 17 przypadków klinicznych. Sześć z nich było przykładami stanów zagrożenia życia. Trzy pytania dotyczyły podstawowych parametrów EKG: częstości pracy serca, osi serca, pochodzenia rytmu serca. Ankietę przeprowadzono przez Internet. Zbadano 551 studentów kierunków lekarskiego, pielęgniarstwa oraz ratownictwa medycznego. Wyniki. Średni wynik osiągnięty przez polskich studentów medycyny był lepszy niż wynik studentów pielęgniarstwa i medycyny ratunkowej. Studenci English Division osiągnęli podobne wyniki. Polscy studenci medycyny byli lepsi od studentów pielęgniarstwa w rozpoznawaniu stanów zagrożenia życia, ale osiągnęli podobne rezultaty do studentów ratownictwa medycznego. Wśród polskich studentów medycyny studenci na IV–VI roku uzyskali lepsze wyniki niż studenci z lat I–III. Samonauczanie EKG zadeklarowało 72% studentów kierunku lekarskiego. Ta grupa osiągnęła lepsze wyniki niż studenci, którzy EKG uczyli się wyłącznie w czasie zajęć na studiach. Mniej niż 20% studentów z każdego kierunku uważało, że zajęć na temat EKG jest wystarczająco dużo. Wnioski. Stan wiedzy studentów kierunków medycznych w Polsce jest niski. Wiele czynników wpływa na umiejętność interpretacji zapisu EKG przez studentów

The potential role of the novel hypothalamic neuropeptides nesfatin-1, phoenixin, spexin and kisspeptin in the pathogenesis of anxiety and anorexia nervosa

Due to the dynamic development of molecular neurobiology and bioinformatic methods several novel brain neuropeptides have been identified and characterized in recent years. Contemporary techniques of selective molecular detection e.g. in situ Real-Time PCR, microdiffusion and some bioinformatics strategies that base on searching for single structural features common to diverse neuropeptides such as hidden Markov model (HMM) have been successfully introduced. A convincing majority of neuropeptides have unique properties as well as a broad spectrum of physiological activity in numerous neuronal pathways including the hypothalamus and limbic system. The newly discovered but uncharacterized regulatory factors nesfatin-1, phoenixin, spexin and kisspeptin have the potential to be unique modulators of stress responses and eating behaviour. Accumulating basic studies revelaed an intriguing role of these neuropeptides in the brain pathways involved in the pathogenesis of anxiety behaviour. Nesfatin-1, phoenixin, spexin and kisspeptin may also distinctly affect the energy homeostasis and modulate food intake not only at the level of hypothalamic centres. Moreover, in patients suffered from anxiety and anorexia nervosa a significant, sex-related changes in the plasma neuropeptide levels occurred. It should be therefore taken into account that the targeted pharmacomodulation of central peptidergic signaling may be potentially helpful in the future treatment of certain neuropsychiatric and metabolic disorders. This article reviews recent evidence dealing with the hypothetical role of these new factors in the anxiety-related circuits and pathophysiology of anorexia nervosa

A different ultrastructural face of ribbon synapses in the rat retina

Abstract Ribbon synapses located exclusively within retinal, cochlear and vestibular connections belong to the most interesting cellular structures but their molecular nature and functions had remained unclear. The study has provided a descriptive morphological analysis of rat eye ribbon synapses using high-resolution transmission electron microscopy (TEM). An original collection of untypical, rarely present in the literature sagittal or tangential sections through the single RIBEYE domain of the particular ribbon have been delivered

The smell of death. State-of-the-art and future research directions

The decomposition of a body is inseparably associated with the release of several types of odors. This phenomenon has been used in the training of sniffer dogs for decades. The odor profile associated with decomposition consists of a range of volatile organic compounds (VOCs), chemical composition of which varies over time, temperature, environmental conditions, and the type of microorganisms, and insects colonizing the carcass. Mercaptans are responsible for the bad smell associated with corpses; however, there are no unified recommendations for conducting forensic analysis based on the detectable odor of revealed corpses and previous research on VOCs shows differing results. The aim of this review is to systematize the current knowledge on the type of volatile organic compounds related to the decomposition process, depending on a few variables. This knowledge will improve the methods of VOCs detection and analysis to be used in modern forensic diagnostics and improve the methods of training dogs for forensic applications

Neuropeptides in the rat claustrum - An immunohistochemical detection

Neuropeptides are involved in numerous brain activities and are responsible for a wide spectrum of higher mental functions. The main purpose of this outline structural qualitative study was to identify the possible immunoreactivity of classical neuropeptides, as well as novel ones such as nesfatin-1, phoenixin (PNX), spexin (SPX), neuromedin U (NMU) and respective receptors within the rat claustrum for the first time. The study shows the novel identification of peptidergic neurotransmission in the rat claustrum which potentially implicates a contribution of this neuropeptide to numerous central neurosecretory mechanisms