Amiloride reduces portal hypertension in rat liver cirrhosis

Objective This study aimed to investigate the effect of amiloride on portal hypertension. Amiloride is known to inhibit Na(+)/H(+) exchangers on activated hepatic stellate cells. Methods Liver cirrhosis in rats was induced by bile duct ligation (BDL) or thioacetamide (TAA) administration. The effects of zymosan for Kupffer cell (KC) activation or a thromboxane (TX) analogue (U46619) were tested in isolated perfused livers of cirrhotic rats and in vivo. Downstream mechanisms were investigated using Rho kinase inhibitor (Y-27632) or amiloride. Acute and chronic effects of amiloride and canrenoate on portal pressure were compared in perfused livers and in vivo. TXB(2) efflux was measured by ELISA. The phosphorylation state of moesin (p-moesin) as an indicator of Rho kinase activity and expression of the thromboxane synthase were assessed by western blot analyses. The activity of hepatic stellate cells was analysed by western blot and staining for alpha-smooth muscle actin (alpha-SMA). Results In BDL rats, KC activation via zymosan increased portal pressure. This was attenuated by the Rho kinase inhibitor Y-27632. Increased thromboxane efflux following zymosan infusion remained unaltered by Y-27632. The infusion of amiloride attenuated zymosan- and U46619-induced increases in portal perfusion pressure. In vivo, direct administration of amiloride, but not of canrenoate, lowered portal pressure. In TAA and BDL rats, treatment with amiloride for 3 days reduced basal portal pressure and KC-induced increases in portal pressure whereas canrenoate had no effect. In livers of amiloride-treated animals, the phosphorylation state of moesin and the number of alpha-SMA positive cells were reduced. Conclusions Amiloride lowers portal pressure in rat liver cirrhosis by inhibition of intrahepatic vasocontraction. Therefore, patients with cirrhosis and portal hypertension may benefit from amiloride therapy

Hypersomnie als Hinweis auf Neuroborreliose

Hypersomnia is known to be associated with symptoms, such as excessive daytime sleepiness, headache, and decreases in vigilance. We report for the first time a patient who initially presented with symptoms for idiopathic hypersomnia but after a thorough diagnostic evaluation was diagnosed as suffering from Lyme disease. This finding stresses the need to potentially include diagnostic tools, like lumbar puncture, in diagnostic procedures, in order to rule out inflammatory diseases of the central nervous system mimicking hypersomnia symptom

Essverhalten, Körpergewicht und Körperzusammensetzung bei Patienten mit Narkolepsie in zeitlichem Zusammenhang mit dem Erkrankungsbeginn

Die Narkolepsie ist charakterisiert durch Hypersomnie mit imperativen Einschlafatta-cken, Kataplexie, Schlafparalyse und hypnagoge Halluzinationen. Man stellte bei Narkolepsiepatienten ein erworbenes zentrales Defizit eines Neuropeptids, des Orexins, fest. Dies scheint bei den Patienten mit einer Reihe weiterer endokriner und metabolischer Auffälligkeiten, unter anderem ei-nem Leptindefizit und Adipositas, verbunden zu sein. In der vorliegenden Studie wurden 500 Narkolepsiepatienten in Deutschland mittels eines Fragebogens befragt, in welchem Alter die vier Kardinalsymptome zum ers-tenmal aufgetreten seien. Es wurde ermittelt, ob sich ihr Appetit, das Verlangen nach Kohlenhydraten und ihr Körpergewicht jeweils im Jahr vor und im Jahr nach Beginn der Symptome verändert habe. Es sollte das Körpergewicht und die Körpergröße angegeben werden. 293 Patienten antworteten. 118 Patienten unterzeichneten weiterhin eine Schweigepflichtsentbindung; so konnte bei diesen die Diagnose Narko-lepsie bestätigt werden. Die Angaben zu Gewicht und Größe ergaben einen mit 68% hohen Anteil an übergewichtigen und adipösen Patienten. Die Auswertung der Fra-gebögen ergab eine signifikant höhere Anzahl an Narkolepsiepatienten, die im Jahr nach Beginn der Symptomatik, im Vergleich zum Jahr davor, über eine Zunahme des Appetits (p=0,020) und Körpergewichts (p=0,009) berichteten. Des Weiteren wurden 28 Betroffene mit anthropometrischen Methoden, der Messung der Körpermaße und –umfänge und der Hautfaltendicke, sowie der Bioimpedanzanalyse bezüglich der Körperzusammensetzung, insbesondere des Körperfettanteils, untersucht. Es konnte gezeigt werden, dass Narkolepsiepatienten mit 27,6 ± 4,8 kg/m2 im Vergleich zum Durchschnitt der deutschen Bevölkerung einen erhöhten BMI und mit einem T-Score von 113,3 ± 9,7 einen erhöhten Bauchumfang aufweisen. Die Körperfettbestimmung ergab mit beiden Methoden einen erhöhten Fettanteil am Körpergewicht (Hautfaltendickemessung: Frauen 41,3 ± 4,6 %, Männer 29,6 ± 5,8 %; BIA: Frauen 46,9 ± 8,1 %, Männer 27,5 ± 4,8 %). In einem weiteren Schritt wurde in dieser Gruppe der Plasmaleptinspiegel gemessen. Die Leptinspiegel lag bei Frauen mit Narkolepsie und einem hohen BMI, signifikant unter der 50 %-Perzentile. Bei einer Kontrollgruppe von 30 Patienten mit Schlafapnoesyndrom wurden ebenfalls Körperzusammensetzung und Leptinspiegel bestimmt. Die Messergebnisse an den Schlafapnoepatienten ergaben keine von den Narkolepsiepatienten signifikant abweichenden Unterschiede. Wir konnten in der vorliegenden Studie zeigen, dass unter Narkolepsiepatienten die Prävalenz an Adipositas hoch ist. Bei übergewichtigen Patienten muss generell mit einer Vielzahl von Begleit- und Folgeerkrankungen gerechnet werden. Zu diesen zählen unter anderem Stoffwechselerkrankungen, Herz-Kreislauferkrankungen und maligne Erkrankungen. Diese Komplikationen korrelieren mit dem Fettverteilungsmuster. Das Gesundheitsrisiko ist bei androider, abdomineller Fettverteilung größer als bei unspezifischer oder gynoider Fettverteilung. Dass das Übergewicht bei Narkolepsiepatienten durch einen hohen Körperfettanteil zustande kommt, konnte durch die Körperfettbestimmung gezeigt werden. Mit der Bestimmung des Taillenumfangs konnte gezeigt werden, dass dieses Fett vermehrt viszeral verteilt ist. Also besteht bei Narkolepsiepatienten mit der stammbetonten Adipositas ein wichtiger Promotor kardiovaskulärer Risikofaktoren und ein eigenständiger Risikofaktor für verschiedene Erkrankungen. Bis heute ist die genaue Genese der Narkolepsie unbekannt. So ist es von Interesse zu wissen, ob die Adipositas ein prämorbides Phänomen ist oder sich mit der Erkran-kung entwickelt. Da im Jahr nach Krankheitsbeginn die mittlere Gewichtszunahme der Patienten um 4 kg höher als im Jahr zuvor war, deuten unsere Ergebnisse auf eine deutliche, sekundäre Gewichtszunahme nach Beginn der Erkrankung bei Narko-lepsiepatienten hin. Diese Erkenntnisse liefern weitere Hinweise dafür, dass bei der Narkolepsie nicht nur der Schlaf-Wach-Rhythmus, sondern auch der Energiestoffwechsel gestört ist. Es ist eine komplexe Störung der Gewichtsregulation, speziell in Bezug auf ein vermindertes Leptinfeedback und die lateralhypothalamische Integration peripherer Signale, anzunehmen

Comparisons of Critical Thermal Maxima and Minima of Juvenile Red Drum (Sciaenops ocellatus) from Texas and North Carolina

The Texas Parks and Wildlife Department was Interested In Identifying cold-tolerant red drum (Sciaenops ocellatus) for a supplemental bay stocking program to help prevent massive fish kills when winter temperatures drop to potentially dangerous levels. Critical thermal maxima (CTMax) and minima (CTMin) of Juvenile red drum from Texas and North Carolina were determined to test for possible geographically based differences In thermal tolerance limits. Juvenile red drum from the two regions acclimated to either 12°C or 20°C exhibited similar thermal tolerance limits while Texas red drum acclimated to 12°C exhibited a statistically higher CTMax, however the observed difference Is not Interpreted as biologically significant. The adjusted mean CTMin for the combined Texas and North Carolina red drum acclimated to 12°C was 1.6°C and adjusted mean CTMax for combined Texas and North Carolina red drum acclimated to 12°C was 29.5°C, and the adjusted mean CTMax for Individuals acclimated to 20°C was 34.8°C. These results suggest red drum from northern and southern parts of the species range have similar temperature tolerances

Comparative monolayer investigations of surface properties of negatively charged glycosphingolipids from vertebrates (gangliosides) and invertebrates (SGL-II, lipid IV).

The surface properties of four negatively charged glycosphingolipids from vertebrates, the sialo-glycosphingolipids (=gangliosides) GM1, GD1a, GT1b and a sulfo-glycosphingolipid (=sulfatide), and of the two negatively charged glycosphingolipids from lower invertebrates, the glucurono-glycosphingolipid Lipid IV and the aminophosphono-glycosphingo-lipid SGL-II were investigated in monolayers at the air/water interface. The molecular peculiarities under investigation were surface pressure (π) and surface potential (ΔV) which are described for Lipid IV and SGL-II for the first time. The surface pressure/area isotherms of all glycosphingolipids were typical of a liquid-expanded monolayer and, with the exception of SGL-II, exhibited a phase transition to a liquid-condensed state at surface pressures above 20 mN/m. The surface potential/molecular area data found for gangliosides in the closely packed state at π=30 mN/m (GM1: ΔV = −17 mV; GD1a: ΔV = −35 mV; GT1b: ΔV = −39 mV) showed only a slight influence of the additional number of negatively charged residues. For Lipid IV, the surface behavior was very similar to GM1 both possessing one negative group per molecule, whereas in SGL-II also the surface potential data (ΔV = −173 mV) were different compared with GD1a both possessing two negative groups per molecule. The addition of Ca2+ condensed the monolayers of all glycolipids and increased the potential in the direction to more positive values, but these findings were less effective in SGL-II films. On the basis of monolayer results presented here, in biological membranes of invertebrates especially Lipid IV might play a similar role as the ganglioside GM1 in vertebrate cells

Surface potentials and electric dipole moments of ganglioside and phospholipid bilayers: Contribution of the polar headgroup at the water/lipid interface.

Monolayers of different gangliosides (GM1, GD1a, GT1b, GMix), ceramide (Cer), sulfatide (Sulf), phospholipids (DOPC, DPPE, DPPS, DOPA), a quaternary ammonium salt (DOMA) and fatty acids (C16, C18, C20) were investigated at the air/water interface on pure water as well as on buffered subphases. Monolayers at the air/water interface consist of two interfaces: the water/lipid and the lipid/air interfaces. The normal components of the effective total dipole moments (Δμ), the effective local dipole moments (Δμα) and effective local surface potentials (ΔVα) of polar headgroups at the water/lipid interface have been calculated from surface potential (ΔV) and mean molecular area (A) measurements of close-packed monolayers. The contribution of the lipid/air interface was previously determined experimentally by partial dipole compensation approach (Vogel, V. and Möbius, D. (1988) Thin Solid Films 159, 73–81). The surface potentials (ΔV) of ganglioside monolayers are quite similar (e.g., GMI = −17 mV, GTib = −39 mV; at surface pressure π = 30 mN/m triethanolamine (TEA)/HCl buffer, pH 7.4, as subphase); this indicates that variations in molecular structure of gangliosides like the influence of the number of negative charges per ganglioside which lead to appreciate changes in the average molecular packing do not cause large changes in surface potential. The local surface potentials (ΔVα) reach to minus several hundred millivolts for nearly all compounds, but clear differences are shown between negatively charged phospholipids (e.g., DPPS = −296 mV at π = 30 mN/m) and glycolipids (e.g., GM1 = −413 mV), and within glycolipids at different surface pressures (e.g., GD1n: − 342 mV at π = 20 mN/m versus −453 mV at π = 30mN/m nly in gangliosides (except for GD1b) the total dipole moments (Δμ) are negative (−0.029 up to − 0.078 D) and directed to the water. Unlike DOPC (+0.069 D) and DOMA (+0.421 D), the local dipole moments (Δμα of all hydrated polar headgroups are negative (e.g., DPPS = −0.331 D; GM1 = −0.729 D) and directed from the monolayer (−) to the water (+). Under well-defined conditions investigated such data are helpful for a better understanding of the large functional role of gangliosides especially in determining the surface potential of biological membranes

Predictive model-based quality inspection using Machine Learning and Edge Cloud Computing

© 2020 The Authors The supply of defect-free, high-quality products is an important success factor for the long-term competitiveness of manufacturing companies. Despite the increasing challenges of rising product variety and complexity and the necessity of economic manufacturing, a comprehensive and reliable quality inspection is often indispensable. In consequence, high inspection volumes turn inspection processes into manufacturing bottlenecks. In this contribution, we investigate a new integrated solution of predictive model-based quality inspection in industrial manufacturing by utilizing Machine Learning techniques and Edge Cloud Computing technology. In contrast to state-of-the-art contributions, we propose a holistic approach comprising the target-oriented data acquisition and processing, modelling and model deployment as well as the technological implementation in the existing IT plant infrastructure. A real industrial use case in SMT manufacturing is presented to underline the procedure and benefits of the proposed method. The results show that by employing the proposed method, inspection volumes can be reduced significantly and thus economic advantages can be generated

Impaired Glucose Tolerance in Sleep Disorders

BACKGROUND: Recent epidemiological and experimental data suggest a negative influence of shortened or disturbed night sleep on glucose tolerance. Due to the high prevalence of sleep disorders this might be a major health issue. However, no comparative studies of carbohydrate metabolism have been conducted in clinical sleep disorders. METHODOLOGY/PRINCIPAL FINDINGS: We performed oral glucose tolerance tests (OGTT) and assessed additional parameters of carbohydrate metabolism in patients suffering from obstructive sleep apnea syndrome (OSAS, N = 25), restless legs syndrome (RLS, N = 18) or primary insomnia (N = 21), and in healthy controls (N = 33). Compared to controls, increased rates of impaired glucose tolerance were found in OSAS (OR: 4.9) and RLS (OR: 4.7) patients, but not in primary insomnia patients (OR: 1.6). In addition, HbA1c values were significantly increased in the same two patient groups. Significant positive correlations were found between 2-h plasma glucose values measured during the OGTT and the apnea-arousal-index in OSAS (r = 0.56; p<0.05) and the periodic leg movement-arousal-index in RLS (r = 0.56, p<0.05), respectively. Sleep duration and other quantitative aspects of sleep were similar between patient groups. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that some, but not all sleep disorders considerably compromise glucose metabolism. Repeated arousals during sleep might be a pivotal causative factor deserving further experimental investigations to reveal potential novel targets for the prevention of metabolic diseases

Co-constructing desired activities : Small-scale activity decisions in occupational therapy

Social inclusion and exclusion are buzzwords in today’s political discourse. While there are many causes of social exclusion, one of the factors repeatedly shown to lead to social exclusion is mental illness, which may hinder people in developing themselves in accordance with their wishes and abilities. Participation is a key dimension of social inclusion—and one that we particularly seek to increase understanding of in this volume. We focus on participation taking place in face-to-face social encounters, seeking to get to the root of the preconditions and consequences of participation by unraveling the interactional processes that underlie what makes it possible. We presuppose that participation in any social or societal sphere presupposes social interaction, which in turn requires the capacity to coordinate with and make sense of others’ actions. Thus, drawing on joint decision-making as a specific arena of social interaction, where the participants’ collaborative management of the turn-by-turn sequential unfolding of interaction can have tangible consequences for the participants’ social and economic circumstances, we seek to increase understanding of the specific vulnerabilities that individuals with mental illness have in this context.In occupational therapy, a therapist and client engage in shared activities that they perform collaboratively during therapeutic sessions. An important part of this joint performance involves providing the client with the opportunity to make short-term decisions on the activities they wish to perform. Analyzing 15 occupational therapy encounters at psychiatric outpatient clinics, in the chapter I explore the functions of these small-scale decisions. The analysis demonstrates that therapists (1) make room for the client’s proposals by shaping the activity context and (2) make proposals themselves on the ways the performance should be accomplished. To summarize, clients are given decision-making power over the content of the activity, whereas therapists use their decision-making power to assist the client’s performance. The analysis shows how small-scale decisions can be employed to construct the occupational performance as shared endeavors and to position the clients as active subjects rather than objects of the professionals’ performance.Peer reviewe

Promoting Client Participation and Constructing Decisions in Mental Health Rehabilitation Meetings

The chapter analyzes practices by which support workers promote client participation in mental health rehabilitation meetings at the Clubhouse. While promoting client participation, the support workers also need to ascertain that at least some decisions get constructed during the meetings. This combination of goals—promoting participation and constructing decisions—leads to a series of dilemmatic practices, the dynamics of which the chapter focuses on analyzing. The support workers may treat clients’ turns retrospectively as proposals, even if the status of these turns as such is ambiguous. In the face of a lack of recipient uptake, the support workers may remind the clients about their epistemic access to the content of the proposal or pursue their agreement or commitment to the idea. These practices involve the support workers carrying primary responsibility over the unfolding of interaction, which is argued to compromise the jointness of the decision-making outcome.The chapter analyzes practices by which support workers promote client participation in mental health rehabilitation meetings at the Clubhouse. While promoting client participation, the support workers also need to ascertain that at least some decisions get constructed during the meetings. This combination of goals—promoting participation and constructing decisions—leads to a series of dilemmatic practices, the dynamics of which the chapter focuses on analyzing. The support workers may treat clients’ turns retrospectively as proposals, even if the status of these turns as such is ambiguous. In the face of a lack of recipient uptake, the support workers may remind the clients about their epistemic access to the content of the proposal or pursue their agreement or commitment to the idea. These practices involve the support workers carrying primary responsibility over the unfolding of interaction, which is argued to compromise the jointness of the decision-making outcome.Peer reviewe