Diagnostic and therapeutic process of respiratory disorders during sleep

Introduction and purpose Sleep apnea is a disturbance of sleep that affects about 10% of adult population and is not easily detected due to unspecific symptoms. The aim of this literature review is to present, respectively, obstructive sleep apnea and central sleep apnea symptoms and integrate the available data in the literature regarding the pathogenesis and treatment methods. Materials and methods A review of literature was performed using PubMed and Google Scholar database. The search criteria included keywords such as sleep apnea, obstructive sleep apnea treatment, central sleep apnea treatment. State of knowledge Sleep disturbances that involve breathing can be categorized as obstructive sleep apnea (OSA) and central sleep apnea. First one is associated with the obstruction of the upper airways and the second one – with malfunctioning breathing generator in the pontomedullary breathing pacemaker. Symptoms are unspecific which makes diagnostic process difficult. However, the right diagnosis and treatment may prevent patients from developing many cardiovascular diseases. Treatment options for OSA include: CPAP, reducing body weight, changing sleep position, braces and surgeries; for CSA: CPAP and acetazolamide. Conclusions OSA and CSA need to be further investigated in order to find more precise ways of diagnosis and treatment, as these diseases remain underreported. It is worth noting, that these conditions predispose to serious diseases, e.g. stroke. Therefore, developing new treatment techniques would beneficial for the health of population

Natriuretic peptide pathways in heart failure in the context of the analysis of the mechanism of action and potential usages of sacubitril/valsartan

Introduction and purpose Heart failure has become a civilization disease, affecting 1-2% of the world's population. It is a condition with various etiologies and phenotypes. The annual mortality rate due to heart failure is approximately 10%, with organ dysfunction caused by hypoperfusion and sudden cardiac death being the leading causes of death. The aim of this study is to present current knowledge of heart failure, focusing on its pathophysiology, and the mechanism of action and applications of sacubitril/valsartan.   Material and methods The following review was based on articles from the PubMed and Google Scholar databases. Key search terms included pathophysiology of heart failure; natriuretic peptide pathways; treatment of heart failure; sacubitril/valsartan.   Conclusions Heart failure is a syndrome marked by the activation of various neurohormonal systems such as the renin-angiotensin-aldosterone system (RAAS), the sympathetic nervous system (SNS) and natriuretic peptides (NP). Historically, the therapeutic approach has focused on reducing RAAS activity and SNS activity. In recent years, increasing attention has been given to potential benefits associated with the NP system. Following disappointing outcomes from studies involving neprilysin (NEP) inhibitors, administered alone or in conjunction with an ACE inhibitor and vasopeptidase inhibitors, there have been findings with the pharmacological class termed ARNI (angiotensin receptor and NEP inhibitors). Sacubitril/valsartan has proven to be an effective and safe treatment that reduces the need for hospitalization, enhances the quality of life and longevity of patients with chronic HFrEF

Asante Calcium Green and Asante Calcium Red—Novel Calcium Indicators for Two-Photon Fluorescence Lifetime Imaging

<div><p>For a comprehensive understanding of cellular processes and potential dysfunctions therein, an analysis of the ubiquitous intracellular second messenger calcium is of particular interest. This study examined the suitability of the novel Ca²⁺-sensitive fluorescent dyes Asante Calcium Red (ACR) and Asante Calcium Green (ACG) for two-photon (2P)-excited time-resolved fluorescence measurements. Both dyes displayed sufficient 2P fluorescence excitation in a range of 720–900 nm. <i>In vitro</i>, ACR and ACG exhibited a biexponential fluorescence decay behavior and the two decay time components in the ns-range could be attributed to the Ca²⁺-free and Ca²⁺-bound dye species. The amplitude-weighted average fluorescence decay time changed in a Ca²⁺-dependent way, unraveling <i>in vitro</i> dissociation constants <i>K</i>_D of 114 nM and 15 nM for ACR and ACG, respectively. In the presence of bovine serum albumin, the absorption and steady-state fluorescence behavior of ACR was altered and its biexponential fluorescence decay showed about 5-times longer decay time components indicating dye-protein interactions. Since no ester derivative of ACG was commercially available, only ACR was evaluated for 2P-excited fluorescence lifetime imaging microscopy (2P-FLIM) in living cells of American cockroach salivary glands. In living cells, ACR also exhibited a biexponential fluorescence decay with clearly resolvable short (0.56 ns) and long (2.44 ns) decay time components attributable to the Ca²⁺-free and Ca²⁺-bound ACR species. From the amplitude-weighted average fluorescence decay times, an <i>in situ K</i>_D of 180 nM was determined. Thus, quantitative [Ca²⁺]_i recordings were realized, unraveling a reversible dopamine-induced [Ca²⁺]_i elevation from 21 nM to 590 nM in salivary duct cells. It was concluded that ACR is a promising new Ca²⁺ indicator dye for 2P-FLIM recordings applicable in diverse biological systems.</p></div

Determination of <i>in situ K</i>_D,t for ACR in salivary duct cells.

<p>(A) Fluorescence decay curves extracted from 2P-FLIM images of ACR-loaded salivary duct cells under Ca²⁺-free (blue, [Ca²⁺]_free  = 0 nM) and Ca²⁺-saturated (red, [Ca²⁺]_free  = 68 µM) conditions and the corresponding global biexponential deconvolution fits with the value. The residuals and individual values of the global biexponential fits are shown below. (B) Normalized amplitudes α_i (squares, solid lines) and amplitude-weighted average fluorescence decay time τ_av,amp (triangles, dashed line). The blue squares correspond to the normalized amplitudes of the short decay time component (0.56 ns, Ca²⁺-free species), whereas the normalized amplitudes of the long decay time component (2.44 ns, Ca²⁺-bound species) are depicted by red squares (N = 11–23). The dotted line marks the determined <i>K</i>_D,t.</p

2P fluorescence excitation spectra for ACR and ACG.

<p>Logarithmic plot of 2P fluorescence excitation action cross-sections Φ_Fσ₂ as a function of excitation wavelength. (A) ACR (means ± SEM, N = 6). (B) ACG (means ± SEM, N = 6). The black circles correspond to the 2P-reference rhodamine B in methanol and data were taken from the literature <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0105334#pone.0105334-Makarov1" target="_blank">[22]</a>. Ca²⁺-free ([Ca²⁺]_free  = 0 nM) and Ca²⁺-saturated ([Ca²⁺]_free  = 40 µM) conditions are depicted by blue and red squares, respectively. (C) Double logarithmic plot of the measured fluorescence intensity <i>I</i>_F as a function of 2P-excitation power <i>P</i> for rhodamine B (black circles) in methanol, ACR (red squares) and ACG (green triangles) in a Ca²⁺-saturated buffer (λ_ex,2P  = 780 nm; N = 3). The data points were fitted by a linear function (<i>r²</i>≥0.98).</p

Behavior of ACR in cockroach salivary glands.

<p>2P-excited (780 nm) fluorescence intensity images of (A) unloaded (1 luminal cuticule, 2 ductal lumen, 3 apically located, point-shaped structures) and (B) ACR-loaded salivary gland ducts (median optical sections). The graphs below the images display the fluorescence intensity traces along the white lines in the images.</p

Steady-state absorption and fluorescence measurements for ACR and ACG.

<p>Chemical structures of (A) ACR and (B) ACG <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0105334#pone.0105334-Hyrc1" target="_blank">[16]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0105334#pone.0105334-Minta1" target="_blank">[27]</a>. Absorption (black) and relative fluorescence (red) spectra in Ca²⁺-free (solid line, [Ca²⁺]_free  = 0 nM) and Ca²⁺-saturated (dashed line, [Ca²⁺]_free  = 40 µM) buffers. (C) ACR (c = 2.5 µM, λ_ex = 540 nm). (D) ACG (c = 0.9 µM, λ_ex = 517 nm). (E) Fluorescence enhancement factor (FEF) of ACR (dashed line) and ACG (solid line) as a function of excitation wavelength. FEF is the ratio of the fluorescence intensities of the excitation spectra under Ca²⁺-saturated conditions and Ca²⁺-free conditions. The curves are the smoothed means of two measurements.</p

Summary of determined parameters of ACR and ACG in comparison to those of OGB-1.

<p>The subscripts <i>f</i> and <i>s</i> correspond to Ca²⁺-free and Ca²⁺-saturated buffer conditions, respectively.</p><p>*λ_ex  = 548 nm.</p><p>**λ_ex  = 525 nm.</p>a<p>Data from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0105334#pone.0105334-Sagolla1" target="_blank">[21]</a>.</p>b<p>Data from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0105334#pone.0105334-Hyrc1" target="_blank">[16]</a>. ^1bData from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0105334#pone.0105334-Hyrc1" target="_blank">[16]</a> (λ_ex  = 540 nm).</p>c<p>Data from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0105334#pone.0105334-Teflabs1" target="_blank">[29]</a>. ^1c Data from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0105334#pone.0105334-Teflabs1" target="_blank">[29]</a> (λ_ex  = 525 nm).</p>d<p>Data from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0105334#pone.0105334-Haugland1" target="_blank">[48]</a>.</p>e<p>As the absolute fluorescence quantum yield Φ_F of ACR and ACG in the Ca²⁺-free buffer were below the limit of detection, they were estimated relatively. Thus, as reference the absolute fluorescence quantum yields of ACR and ACG in Ca²⁺-saturated buffer were used <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0105334#pone.0105334-FeryForgues1" target="_blank">[25]</a>.</p

Time-resolved fluorescence recordings of ACR and ACG after 2P-excitation at 780 nm.

<p>Fluorescence decay curves of (A) ACR and (B) ACG in Ca²⁺-free (blue, [Ca²⁺]_free  = 0 nM) and Ca²⁺-saturated (red, [Ca²⁺]_free  = 40 µM) buffer solutions and the corresponding global biexponential deconvolution fits with values; IRF: instrument response function (black). The black arrow indicates increasing [Ca²⁺]_free. The residuals and individual values of the global biexponential fits are shown below. Normalized amplitudes α_i (squares, solid lines) and amplitude-weighted average fluorescence decay time τ_av,amp (triangles, dashed line) as a function of [Ca²⁺]_free for (C) ACR and (D) ACG. The blue squares correspond to the normalized amplitudes of the short decay time component (ACR: 0.12 ns±0.006 ns and ACG: 0.25 ns±0.04 ns; Ca²⁺-free species), whereas the normalized amplitudes of the long decay time component (ACR: 0.57 ns±0.003 ns and ACG: 2.38 ns±0.02 ns; Ca²⁺-bound) are depicted by red squares, (means ± SEM, N = 5).</p

Active zone protein expression changes at the key stages of cerebellar cortex neurogenesis in the rat

Signal transduction and neurotransmitter release in the vertebrate central nervous system are confined to the structurally complex presynaptic electron dense projections called "active zones." Although the nature of these projections remains a mystery, genetic and biochemical work has provided evidence for the active zone (AZ) associated proteins i.e. Piccolo/Aczonin, Bassoon, RIM1/Unc10, Munc13/Unc13, Liprin-alpha/SYD2/Dliprin and ELKS/CAST/BRP and their specific molecular functions. It still remains unclear, however, what their precise contribution is to the AZ assembly. In our project, we studied in Wistar rats the temporal and spatial distribution of AZ proteins and their colocalization with Synaptophysin in the developing cerebellar cortex at key stages of cerebellum neurogenesis. Our study demonstrated that AZ proteins were already present at the very early stages of cerebellar neurogenesis and exhibited distinct spatial and temporal variations in immunoexpression throughout the course of the study. Colocalization analysis revealed that the colocalization pattern was time-dependent and different for each studied protein. The highest collective mean percentage of colocalization (>85%) was observed at postnatal day (PD) 5, followed by PD10 (>83%) and PD15 (>80%). The findings of our study shed light on AZ protein immunoexpression changes during cerebellar cortex neurogenesis and help frame a hypothetical model of AZ assembly. (C) 2013 Elsevier GmbH. All rights reserved