A ocorrência de disfunção renal em pacientes com insuficiência cardíaca descompensada é evento comum e associado a pior prognóstico. Entretanto, intervenções direcionadas a prevenção e tratamento da disfunção renal nestas circunstâncias revelaram resultados desapontadores. O objetivo deste estudo foi investigar o efeito da solução salina hipertônica (SSH) para a prevenção de disfunção renal em pacientes com insuficiência cardíaca descompensada. Trata-se de ensaio clínico duplo-cego e randomizado no qual pacientes com insuficiência cardíaca descompensada foram alocados para receber 100 ml de SSH (NaCl 7,5%) ou placebo (NaCl 0,9%) duas vezes ao dia por três dias. O desfecho primário foi a elevação igual ou superior a 0,3 mg/dl da creatinina sérica; o desfecho secundário foi a elevação de biomarcadores da função renal, e incluiu creatinina, cistatina C, lipocalina de neutrófilos associada a gelatinase (NGAL), excreção urinária da isoforma A1 do transportador de uréia, da isoforma 3 do trocador de Na+/H+ e de aquaporina 2 . Ao todo, 22 pacientes foram alocados no grupo SSH e 12 no grupo placebo. O desfecho primário ocorreu em 2 (10%) pacientes no grupo SSH e em 6 (50%) pacientes no grupo placebo (risco relativo 0,3; intervalo de confiança 95% de 0,09 a 0,98; P=0,01). Ao longo da intervenção, a concentração sérica tanto de creatinina como de cistatina C mantiveram-se estáveis no grupo HSS e elevaram-se no grupo placebo (p=0,004 e p=0,03, respectivamente). Não houve diferença estatisticamente significativa entre os grupos em relação à concentração sérica de NGAL. A expressão urinária dos transportadores de membrana de células tubulares esteve aumentada no grupo SSH em comparação ao grupo placebo, tanto para a isoforma A1 do transportador de uréia, quanto para a isoforma 3 do trocador de Na+/H+ e da isoforma 2 da aquaporina .Nossos dados permitem concluir que a administração de SSH pode atenuar a ocorrência de disfunção renal em pacientes com insuficiência cardíaca descompensada, por atuar na função tubular e na glomerular, achado com importantes implicações clínicas. / The occurrence of renal dysfunction is frequent among patients with decompensated heart failure and is associated with increased mortality. However, interventions targeted to prevention of renal dysfunction in this setting have been disappointing. The objective of this study was to investigate the effects of hypertonic saline solution for prevention of renal dysfunction in patients admitted for decompensated heart failure. This study is a double-blind randomized trial, in which patients with decompensated heart failure were assigned to receive a three-day course of 100ml of hypertonic saline solution (HSS - NaCl 7.5%) twice daily or placebo. The primary end point was an increase in serum creatinine of 0.3mg/dL or more. Main secondary end points were changes in biomarkers of renal function, including serum levels of creatinine, cystatine C, neutrophil gelatinase-associated lipocalin (NGAL) and the urinary excretion of aquaporin 2, urea transporter A1, and sodium/hydrogen exchanger 3. Altogether, 22 patients were assigned to HSS and 12 to placebo. The primary end point occurred in two (10%) patients in HSS group and six (50%) in placebo group (relative risk 0.3; 95% CI 0.09 - 0.98; P=0.01). Relative to baseline, serum creatinine and cystatin C levels were lower in HSS as compared to placebo (P=0.004 and 0.03, respectively). NGAL level was not statistically different between groups, however the urinary expression of aquaporin 2, urea transporter A1, and sodium/hydrogen exchanger 3 were significantly higher in HSS than in placebo. Therefore, the present data suggest that the administration of hypertonic saline solution to patients with decompensated heart failure may attenuate heart failure-induced acute kidney injury as indicated by improvement in both glomerular and tubular defects, a finding with important clinical implications.

Autosomal recessive triple A syndrome is caused by mutations in the AAAS gene encoding the protein ALADIN. The disorder manifests with the triad of adrenocorticotropin-resistant adrenal insufficiency, achalasia of the stomach cardia and impaired tear production (alacrima) in combination with progressive neurological impairment of the central, peripheral and autonomic nervous systems. ALADIN is part of the nuclear pore complex acting as a scaffold nucleoporin. In this work the role of ALADIN in the human adrenocortical tumour cell line NCI-H295R1 was investigated. These cells were engineered to either over-express or down-regulate AAAS by inducible stable transfection. Alterations in steroidogenic gene expression and functional consequences were determined. In addition, the role of ALADIN on cell viability and oxidative stress response was analysed. Using both the human adrenal NCI-H295R1-TR AAAS knock-down and over-expression models the potential impairment of the nuclear import of aprataxin, DNA ligase 1 and ferritin heavy chain 1 was investigated. For this YFP-specific vectors transiently transfected into the cell lines were employed. The findings indicate that AAAS knock-down induces a down-regulation of genes coding for type II microsomal cytochrome P450 hydroxylases CYP17A1 and CYP21A2 and their electron donor enzyme cytochrome P450 oxidoreductase, thereby decreasing biosynthesis of precursor metabolites required for glucocorticoid and androgen production. Furthermore I demonstrate that ALADIN deficiency leads to increased susceptibility to oxidative stress and alteration in redox homeostasis after paraquat treatment. Finally, I show significantly impaired nuclear import of DNA ligase 1, aprataxin and ferritin heavy chain 1 in ALADIN knock-down cells. I conclude that down-regulating ALADIN results in decreased oxidative stress response leading to alteration in steroidogenesis, highlighting the knock-down cell model as an important in vitro tool for studying the adrenal phenotype in triple A syndrome. In an approach to identify new interaction partners of ALADIN, co-immunoprecipitation followed by proteome analyses using mass spectrometry was conducted in a GFP-ALADIN over-expression model using the human adrenocortical tumor cell line NCI-H295R. These results were verified in co-immunoprecipitation assays of endogenous ALADIN using NCI-H295R wild-type cells. The results suggest a possible interaction between ALADIN and microsomal flavoprotein cytochrome P450 oxidoreductase and progesterone receptor membrane compartment 2. Co-localisation analyses of these findings were done using immunofluorescence. The data are suggestive for an involvement of ALADIN in the export of nuclear-encoded mitochondrial proteins. Regulation of adrenocortical steroidogenesis is complex and there is increasing evidence that oxidative stress due to ROS accumulation and mitochondria are significantly involved. Furthermore, there may be an important cross-talk between functional organelles comprising nucleus, ER and mitochondria which presumably involves lipid metabolism. The goal of this work was to elucidate the function of ALADIN for the cellular oxidative stress response and its possible consequences for adrenocortical steroidogenesis in triple A syndrome patients. / Mutationen im AAAS Gen verursachen die autosomal rezessive Krankheit Triple-A-Syndrom. AAAS kodiert das Nukleoporin ALADIN, welches Bestandteil des nukleären Porenkomplexes ist. Phänotypische Charakteristika des Triple-A-Syndroms sind Nebennierenrinden-Insuffizienz, Achalasie des unteren Speiseröhrenschließmuskels und eine fehlende Tränenproduktion (Alakrimie). Diese Symptome sind kombiniert mit progredienten neurologischen Störungen des zentralen, peripheren und autonomen Nervensystems. In dieser Arbeit wurde die Rolle von ALADIN in der humanen Karzinom-Zelllinie NCI-H295R1 untersucht. Diese Nebennierenrinden-Zellen wurden stabil transfiziert und mit einem induzierbaren Expressionssystem modifiziert, so dass sie AAAS entweder überexprimierten oder herunterregulierten. In NCI-H295R1-Zellen wurden Veränderungen der Genexpression von Enzymen der Steroidogenese und funktionelle Konsequenzen der Überexpression oder Herunterregulation von ALADIN gemessen. Des Weiteren wurde die Rolle von ALADIN auf die Zellviabilität und die Redox-Homöostase analysiert. ALADIN überexprimierende und herunterregulierte Zellen wurden verwendet, um die potentielle Behinderung des nukleären Imports von Proteinen zu untersuchen, welche den Zellkern gegen oxidativen Stress schützen (z.B. Aprataxin, DNA-Ligase 1 und Ferritin Heavy Chain 1). Dazu wurden YFP-spezifische Vektoren transient in diese Zellen gebracht. Mit den Ergebnissen dieser Arbeit wurde gezeigt, dass die Herunterregulation von AAAS eine Verminderung der Genexpression von CYP17A1 und CYP21A2 und deren Elektronendonor Cytochrom P450 Oxidoreduktase bewirken. Die Biosynthese der Vorläufermetabolite von Kortisol und Aldosteron ist in diesen Zellen ebenfalls vermindert. Des Weiteren zeigen die ALADIN-defizienten NCIH295R1-Zellen eine erhöhte Sensitivität gegenüber oxidativem Stress und eine veränderte Redox-Homöostase nach der Behandlung mit Paraquat. Darüber hinaus konnte in dieser Studie auch gezeigt werden, dass herunterregulierte ALADIN NCI-H295R1-Zellen einen verminderten Zellkernimport von Aprataxin, DNA-Ligase 1 und Ferritin heavy chain 1 besitzen. Aus diesen Ergebnissen kann geschlussfolgert werden, dass ALADIN-defiziente Nebennierenzellen eine verminderte Stressantwort auf oxidativen Stress besitzen; dies führt schlussendlich zu einer veränderten Steroidogenese. Das beschriebene ALADIN knock-down Modell in NCI-H295R1-Zellen ist ein wichtiges in vitro Werkzeug, um die Pathogenese der Nebennierenveränderungen im Triple-A-Syndrom zu erforschen. Neue Interaktionspartner von ALADIN wurden mit Hilfe von Co-Immunpräzipitation gefolgt von Proteom-Analysen durch Massenspektrometrie in einem GFP-ALADIN Überexpressionsmodell in NCI-H295R charakterisiert. Die Ergebnisse wurden durch Experimente auf endogenem Niveau in NCI-H295R-Wildtypzellen verifiziert. Mit diesen Daten wird in dieser Arbeit erstmals eine Interaktion zwischen ALADIN und dem Flavoprotein Cytochrom P450 Oxidoreduktase und Progesterone Receptor Membrane Compartment 2 nachgewiesen. Diese Ergebnisse wurden mit Co-Lokalisierungsanalysen durch Immunfluoreszenzfärbung von ALADIN und Cytochrome P450 Oxidoreduktase ergänzt. Außerdem gibt die Arbeit Hinweise darauf, dass ALADIN als Nukleoporin an dem nuklearen Export mitochondrialer Vorläuferproteine beteiligt ist. Die Regulation der Steroidogenese in der Nebennierenrinde ist komplex und es existieren zahlreiche Hinweise darauf, dass oxidativer Stress aufgrund der Ansammlung reaktiver Sauerstoffradikale und. dass die Mitochondrien involviert sind. Außerdem ist ein funktionelles Zusammenspiel verschiedener Organellen, darunter Nukleus, ER und Mitochondrien, von großer Bedeutung. Das Ziel dieser Arbeit war die Identifizierung der Funktion von ALADIN in der zellulären oxidativen Stressantwort und die möglichen Konsequenzen für die Steroidogenese in der Nebennierenrinden in Triple-A-Syndrom-Patienten.

SAMMANFATTNING    Bakgrund: Venösa bensår är ett globalt vanligt förekommande fenomen, 1–2 % av jordens befolkning anses vara drabbade. Bensår skapar stort lidande för patientens fysiska och psykiska hälsa. Två vanliga förekommande problem är smärta och isolering. Det finns flera metoder för att läka venösa bensår där flerlagers-kompressionslinda anses vara en av det bästa metoderna. Att läka bensår skulle kunna minska patientlidandet.    Syfte: Att sammanställa och jämföra läkningseffekten av två- och fyra-lagerskompressionslindning hos patienter med venösa bensår.   Metod: En deskriptiv design med litteraturöversikt användes som metod där tio vetenskapliga kvantitativa originalartiklar inkluderades. Artikelsökning gjordes i databaserna PubMed och CINAHL.   Resultat: Litteraturöversikten kunde inte påvisa en skillnad mellan 2LB- och 4LB-kompressiongrupperna för förbättrad och fullständig läkningsförmåga. Båda lindorna bekräftades ha en sårläkande effekt. Effekten av kompressionslindorna gav en mer påskyndad sårläkning, än hos patienter utan kompressionsbehandling. Majoriteten av de inkluderade studierna visade på ett liknande resultat i fullständig procentuell läkning mellan två-lagerkompressionslindning (2LB) och fyra-lagerkompressionslindning (4LB).   Slutsats: Litteraturöversikten visar att kompressionsbehandling med 2LB och 4LB har en likvärdig och god sårläkande effekt för patienter. Både 2LB och 4LB är mer gynnsam för sårläkning och välmående än utan kompressionsbehandling för patienter som lever med venösa bensår. / ABSTRACT Background: Venous leg ulcers is a globally common phenomenon, 1-2 % of the world’s population is believed to be affected. Leg ulcers causes great suffering for the patient's physical and mental health. Two common complications are pain and isolation. There are several methods to heal venous leg ulcers, multilayer-compression-therapy is considered one of the best methods. Healing leg ulcers could reduce patient suffering. Purpose: To compile and compare the healing effects of two- and four-layer compression therapy in patients with venous leg ulcers.   Method: A descriptive design with a literature review as method, with ten scientific quantitative original articles were included. Article searches was done in databases PubMed and CINAHL.   Results: The results did not show a difference between the 2LB and 4LB-groups regarding complete and improved healing. However, both methods had a healing effect. The bandages were more effective in accelerating healing in patients, than in patients without compression therapy. Most of the included studies showed a similar result in the percentage of complete healing effect between the two-layer compression therapy (2LB) and four-layer compression therapy (4LB).   Conclusion: This literature review demonstrated that compression therapy with 2LB and 4LB has an equally as well as good healing effect for patients. Both 2LB and 4LB are significantly more beneficial for wound healing and well-being than without compression therapy for patients living with venous leg ulcers.

Gap Junction Kanäle sind wesentlich für die interzelluläre Kommunikation im Herzen. Die wichtigsten kardialen Gap Junction Proteine sind Connexin 43, Connexin 40 und in frühen Entwicklungsstadien Connexin 45. Da Katecholamine eine wichtige Rolle in der kardialen Physiologie bzw. Pathophysiologie spielen, sollte geklärt werden, ob Katecholamine die Expression von Connexin 40 und Connexin 43 beeinflussen. Es wurden neonatale Rattenkardiomyozyten in Zellkultur 24 Stunden mit aufsteigenden Noradrenalinkonzentrationen (1-10000 nM) (physiologischer Agonist für α-und β-Adrenozeptoren) inkubiert. Hier zeigte sich ein signifikanter Anstieg der Connexin 43 Expression, während die Connexin 40 Expression nicht beeinflußt wurde. Um zu zeigen über welchen Adrenozeptor (α oder β) die Hochregulation von Cx 43 durch Noradrenalin erfolgt, wurden die Zellkulturen in zwei weiteren Versuchsreihen zusätzlich mit einem β-Blocker (Propranolol 100µM) bzw. einem α- Blocker (Prazosin 10 µM) über 24 Std. inkubiert. Hier zeigte sich eine deutliche Inhibierung des Noradrenalineffektes durch die Blockade der α-Rezeptoren durch Prazosin. Eine Blockade der β-Rezeptoren hatte keinen inhibitorischen Effekt auf die Hochregulation der Expression von Cx 43 durch Noradrenalin. Es kam hier sogar zu einer verstärkten Expression verglichen mit der Cx 43 Expression unter Noradrenalin ohne Rezeptorblockade. Desweiteren wurde überprüft, ob es auch unter der Behandlung von Sprague– Dawley-Ratten mit einem β-Mimetikum (Isoprenalin) bzw. einem α-Mimetikum (Phenylephrin) zu einer Veränderung der Connexinexpression kommt. Die Western Blot Analysen ergaben hierbei wieder einen α-Rezeptoren vermittelten Effekt, indem es zu einem wesentlichen Konzentrationsanstieg von Connexin 43 unter der Behandlung mit Phenylephrin kam.

IntroductionThe young adult patients with aortic valve insufficiency undergo aortic valve replacement (AVR) and are forced to take anticoagulation medications for the rest of life due to prosthetic valve. This leads to many post-operative complications and drastic outcomes. Whereas, the in-vogue alternative of aortic valve repair (AVr) is available and a lot more beneficial as well.Especially considering the surgeon’s skills for selected repair procedure, selectively chosen patient with mild to moderate grades of aortic valve insufficiency and no significant comorbidities present for at least five (5) years or longer time. AimThe aim of this study was to affirm ‘if all kind of outcomes of aortic valve repair are beneficial alternative to aortic valve replacement (AVR) for the patients suffering from aortic valve insufficiency for at least five (5) years or longer time. Material and MethodsInternet search using standard key words of ‘Aortic Valve Repair and Outcomes’ was used to find both white literature (officially published literature) and grey literature (unpublished or ongoing study/literature) with human, adult, English language and studies published after January 1st 2007 as limitations. Inclusion criteria was adult patients with aortic insufficiency with aortic valve repair as intervention with outcomes at least greater than five (5) years were considered. All the data was extracted using Microsoft excel for windows and was analyzed using GraphPad Prisma. Results20 studies comprising of 5369 patients were included in this systemic review, which included 2 randomized control trails, 7 clinical prospective studies, 8 retrospective studies and 3 observational studies. ConclusionThis study suggests that aortic valve repair is a beneficial alternative available for younger adults suffering from aortic valve insufficiency in longer time.

This critical synopsis of prior work by Clive Beggs is submitted in support of a PhD by published work. The work focuses on venous and cerebrospinal fluid (CSF) anomalies associated with multiple sclerosis (MS) and other neurological diseases. MS is characterized by focal inflammatory lesions, which are often venocentric. Recently a vascular syndrome, chronic cerebrospinal venous insufficiency (CCSVI) has been linked with MS. This syndrome, which is characterized by constricted cerebral venous outflow, has become mired in controversy, with various studies producing conflicting findings, with the result that the science associated with CCSVI has become obscured. Clive Beggs work seeks to bring clarity to the debate surrounding CCSVI by characterizing physiological changes associated with constricted cerebral venous outflow. The work submitted here involves collaborative studies with Robert Zivadinov (University of Buffalo), Paolo Zamboni (University of Ferrara), and Chih- Ping Chung (National Yang Ming University of Medicine). The key findings of these studies are: (i) MS patients, diagnosed with CCSVI, exhibit greatly increased hydraulic resistance of the cerebral venous drainage system; (ii) MS patients experience loss of the small cerebral veins; (iii) MS patients exhibit reduced CSF bulk flow, consistent with mild venous hypertension; (iv) MS patients exhibit increased CSF pulsatility in the Aqueduct of Sylvius, which appears to be linked with mild venous hypertension associated with CCSVI; and (v) jugular venous reflux is associated with white matter and parenchymal volumetric changes in Alzheimer’s patients. Collectively, these findings suggest that extracranial venous anomalies are associated with changes in the intracranial physiology.

(1) Background: Patients with severe chronic kidney disease (CKD G4–G5) often have chronically elevated high-sensitivity cardiac troponin T (hs-cTnT) values above the 99th percentile of the upper reference limit. In these patients, optimal cutoff levels for diagnosing non-ST-elevation acute coronary syndrome (NSTE-ACS) requiring revascularization remain undefined. (2) Methods: Of 11,912 patients undergoing coronary angiography from 2012 to 2017 for suspected NSTE-ACS, 325 (3%) had severe CKD. Of these, 290 with available serial hs-cTnT measurements were included, and 300 matched patients with normal renal function were selected as a control cohort. (3) Results: In the CKD cohort, 222 patients (76%) had NSTE-ACS with indication for coronary revascularization. Diagnostic performance was high at presentation and similar to that of the control population (AUC, 95% CI: 0.81, 0.75–0.87 versus 0.85, 0.80–0.89, p = 0.68), and the ROC-derived cutoff value was 4 times higher compared to the conventional 99th percentile. Combining the ROC-derived cutoff levels for hs-cTnT at presentation and absolute 3 h changes, sensitivity increased to 98%, and PPV and NPV improved up to 93% and 86%, respectively. (4) Conclusions: In patients with severe CKD and suspected ACS, the diagnostic accuracy of hs-cTnT for the diagnosis of NSTE-ACS requiring revascularization is improved by using higher assay-specific cutoff levels combined with early absolute changes.

No description available.

No description available.

Gostovic, M & Grube, R. Livet med venösa bensår. En litteraturstudie. Examensarbete i omvårdnad 15 högskolepoäng. Malmö Universitet: Fakulteten för Hälsa och Samhälle, Institutionen för Vårdvetenskap, 2022.   Bakgrund: Venösa bensår beror på venös insufficiens som är en kronisk sjukdom som orsakar cirkulatorisk svikt i de nedre extremiteterna och drabbar främst den äldre befolkningen. De venösa bensåren uppkommer ofta på grund av trombos, yttre trauma, fysisk inaktivitet eller hereditet. Det är vanligt med samsjuklighet vid venös insufficiens. Behandlingen består främst av omläggning och livslång kompressionsbehandling. Syfte: Syftet med litteraturstudien var att undersöka patienters upplevelser av att leva med venösa bensår. Metod: En litteraturstudie som är baserad på resultat från 13 empiriska studier med kvalitativ ansats från Cinahl, PubMed och PsycInfo. Studierna har granskats med hjälp av Kvalitetsgranskningsmall för studier med kvalitativ forskningsmetodik och de inkluderade studierna har bedömts vara av hög samt medelhög kvalitet. De inkluderade studiernas resultat analyserades med hjälp av integrerad sammanställning av kvalitativ forskning inspirerad av metasyntes. Resultat: Sex teman identifierades: Egenvårdens betydelse för välbefinnandet, Svårigheter i egenvården, Vården som en del av vardagen, Upplevelsen av smärta, Upplevd självbild och skam samt Social och psykisk påverkan. Konklusion: Litteraturstudien gav en ökad förståelse för vad det innebär att leva med venösa bensår och gav en insikt i vilka kunskapsluckor som vården behöver fylla för att kunna förse patienterna med en adekvat omvårdnad. / Gostovic, M & Grube, R. Life with venous leg ulcers. A Literature Review. Degree project in nursing 15 credit points. Malmö University: Faculty of Health and Society, Department of Care Science, 2022.   Background: Venous leg ulcers is caused by venous insufficiency which is a chronic disease caused by circulatory deficiency in the lower extremities and affects primarily the elderly population. The venous leg ulcers most commonly originates from thrombosis, external trauma, physical inactivity or heredity. Comorbidity is common among the patients with venous leg ulcers.  The treatment plan primarily consists of wound dressing and lifelong compression treatment. Aim: The aim of the study was to investigate the patients’ experiences of living with venous leg ulcers. Method: A literature review based on results from 13 empirical studies with qualitative design from Cinahl, PubMed and PsycInfo. The studies have been reviewed by using a review template intended for qualitative studies and the included studies were valued as high and medium high quality. The included studies results were analyzed with the help of an integrated compilation of qualitative research inspired by meta synthesis. Results: Six themes were identified: Self-care had an impact of the well-being, Health care as a part of the daily life, The experience of pain, Perceived self-image and shame and Social and psychological influence. Conclusion: The literature review increased the understanding of what it’s like to live with venous leg ulcers and gave an insight into which knowledge-gaps the health care needs to fill to provide the patients with adequate care.