Effect of cardiac rehabilitation following coronary bypass surgery or other coronary interventions

Efst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinnInngangur: Hjartaendurhæfing er viðurkennd meðferð hjá sjúklingum með kransæðasjúkdóma en takmarkaðar upplýsingar eru til um hana á Íslandi. Markmið þessarar rannsóknar var að kanna hvort hjartaendurhæfing á stigi II í HL-stöðinni eftir kransæðahjáveituaðgerð eða kransæðavíkkun, skilaði bættri líkamlegri heilsu og betri lífsgæðum til sjúklinga. Efniviður og aðferðir: Sjúklingar sem gengist höfðu undir inngrip vegna kransæðasjúkdóms var boðin þátttaka. Alls þáðu 64 boðið (af 65) en 48 luku þátttöku í rannsókninni. Að meðaltali mættu þátttakendur í 2,1 skipti á viku í 8,4 vikur. Mælingar gerðar: þrektala (W/kg), blóðþrýstings- og púlssvörun úr áreynsluprófi og líkamsþyngdarstuðull (kg/m2). Til að meta heilsutengd lífsgæði var notaður SF-36v2 lífsgæðakvarðinn. Niðurstöður: Þrek batnaði um 14,4% (p<0,001) og 6,1% aukning varð á hámarkspúlsi (p=0,001). Þátttakendum var skipt upp í tvo hópa eftir aldri (32-64 ára og 65-86 ára) og bættu báðir aldurshópar sig svipað í þreki (14,6% og 14,1%) en það var eingöngu eldri hópurinn sem jók hámarkspúls marktækt eða um 7,2% (p=0,007). Þegar þátttakendum var skipt í tvo hópa eftir því hversu oft þeir æfðu á viku kom fram 10,1% aukning á þrektölu hjá hópnum sem æfði sjaldnar en 19,8% hjá þeim sem æfðu oftar (p<0,001). Þátttakendur mátu líkamlega líðan, mælda með spurningalista um lífsgæði, betri við lok þjálfunar (p=0,003) en ekki andlega líðan (p=0,314). Þegar þátttakendum var skipt í tvo hópa eftir því hvernig þeir mátu líkamlega líðan í upphafi rannsóknar varð marktæk hækkun um 15,1% á líkamlegri líðan hjá þeim sem mátu sig í verri stöðu í upphafi (p=0,002), en hinn hópurinn hækkaði um 1,2%. Ályktun: Hjartaendurhæfing bætir þrek og líkamlega vellíðan. Magn þjálfunar hefur áhrif á bætingu í þreki.Introduction: Cardiac rehabilitation is a well-established treatment for patients with coronary artery disease but limited information is available for Icelandic patients. The aim of this study was to investigate whether Phase II cardiac rehabilitation at the HL rehabilitation center was improving physical health and quality of life of patients. Material and methods: Patients that had undergone coronary artery intervention were invited to participate. There were 64 participants (of 65 invited) that started in the study and 48 that finished. On average participants attended 2.1 sessions pr. week, for 8.4 weeks. Measurements performed: endurance (W/kg), blood pressure and pulse responses from an exercise test and body mass index (kg/m2). To measure health related quality of life the SF-36v2 questionnaire was used. Results: Endurance improved by 14.4% (p<0,001) and a 6.1% increase was seen in peak pulse (p=0.001). The group was divided by age (32-64 years and 65-86 years) and both age groups improved their endurance number similarly (14.6% and 14.1%) but only the older age group improved peak pulse significantly or 7.2% (p=0.007). When the group was divided according to number of training sessions per week there was a 10.1% increase in endurance in the group that had fewer sessions but it was 19.8% in those that attended more sessions (p<0.001). Participants assessed that their physical health, measured with a questionnaire, had improved at the end of training (p=0.003). When the group was divided into two groups according to how they measured their physical health at the beginning of the study there was a significant increase of 15.1% in physical health in those that estimated worse quality of life at the beginning of the study, but the other group had an increase of 1.2%. Conclusion: Cardiac rehabilitation improves endurance and physical wellbeing in patients. Training magnitude is essential for improvement

MAPK Kinase Kinase-1 Is Essential for Cytokine-Induced c-Jun NH2-Terminal Kinase and Nuclear Factor-κB Activation in Human Pancreatic Islet Cells

OBJECTIVE—The transcription factor nuclear factor-κB (NF-κB) and the mitogen-activated protein kinases (MAPKs) c-Jun NH2-terminal kinase (JNK) 1/2 are known to play decisive roles in cytokine-induced damage of rodent β-cells. The upstream events by which these factors are activated in response to cytokines are, however, uncharacterized. The aim of the present investigation was to elucidate a putative role of the MAPK kinase kinase-1 (MEKK-1) in cytokine-induced signaling

A high-affinity, bivalent PDZ domain inhibitor complexes PICK1 to alleviate neuropathic pain

Maladaptive plasticity involving increased expression of AMPA‐type glutamate receptors is involved in several pathologies, including neuropathic pain, but direct inhibition of AMPARs is associated with side effects. As an alternative, we developed a cell‐permeable, high‐affinity (~2 nM) peptide inhibitor, Tat‐P$_4$‐(C5)$_2$, of the PDZ domain protein PICK1 to interfere with increased AMPAR expression. The affinity is obtained partly from the Tat peptide and partly from the bivalency of the PDZ motif, engaging PDZ domains from two separate PICK1 dimers to form a tetrameric complex. Bivalent Tat‐P$_4$‐(C5)$_2$ disrupts PICK1 interaction with membrane proteins on supported cell membrane sheets and reduce the interaction of AMPARs with PICK1 and AMPA‐receptor surface expression in vivo. Moreover, Tat‐P$_4$‐(C5)$_2$ administration reduces spinal cord transmission and alleviates mechanical hyperalgesia in the spared nerve injury model of neuropathic pain. Taken together, our data reveal Tat‐P$_4$‐(C5)$_2$ as a novel promising lead for neuropathic pain treatment and expand the therapeutic potential of bivalent inhibitors to non‐tandem protein–protein interaction domains

Compilation of a panel of informative single nucleotide polymorphisms for bovine identification in the Northern Irish cattle population

<p>Abstract</p> <p>Background</p> <p>Animal identification is pivotal in governmental agricultural policy, enabling the management of subsidy payments, movement of livestock, test scheduling and control of disease. Advances in bovine genomics have made it possible to utilise inherent genetic variability to uniquely identify individual animals by DNA profiling, much as has been achieved with humans over the past 20 years. A DNA profiling test based on bi-allelic single nucleotide polymorphism (SNP) markers would offer considerable advantages over current short tandem repeat (STR) based industry standard tests, in that it would be easier to analyse and interpret. In this study, a panel of 51 genome-wide SNPs were genotyped across panels of semen DNA from 6 common breeds for the purposes of ascertaining allelic frequency. For SNPs on the same chromosome, the extent of linkage disequilbrium was determined from genotype data by Expectation Maximization (EM) algorithm. Minimum probabilities of unique identification were determined for each breed panel. The usefulness of this SNP panel was ascertained by comparison to the current bovine STR Stockmarks II assay. A statistically representative random sampling of bovine animals from across Northern Ireland was assembled for the purposes of determining the population allele frequency for these STR loci and subsequently, the minimal probability of unique identification they conferred in sampled bovine animals from Northern Ireland.</p> <p>Results</p> <p>6 SNPs exhibiting a minor allele frequency of less than 0.2 in more than 3 of the breed panels were excluded. 2 Further SNPs were found to reside in coding areas of the cattle genome and were excluded from the final panel. The remaining 43 SNPs exhibited genotype frequencies which were in Hardy Weinberg Equilibrium. SNPs on the same chromosome were observed to have no significant linkage disequilibrium/allelic association. Minimal probabilities of uniquely identifying individual animals from each of the breeds were obtained and were observed to be superior to those conferred by the industry standard STR assay.</p> <p>Conclusions</p> <p>The 43 SNPs characterised herein may constitute a starting point for the development of a SNP based DNA identification test for European cattle.</p

Overexpression of SIRT1 Protects Pancreatic β-Cells Against Cytokine Toxicity by Suppressing the Nuclear Factor-κB Signaling Pathway

OBJECTIVE—SIRT1, a class III histone/protein deacetylase, is known to interfere with the nuclear factor-κB (NF-κB) signaling pathway and thereby has an anti-inflammatory function. Because of the central role of NF-κB in cytokine-mediated pancreatic β-cell damage, we postulated that SIRT1 might work in pancreatic β-cell damage models

JunB Inhibits ER Stress and Apoptosis in Pancreatic Beta Cells

Cytokines contribute to pancreatic β-cell apoptosis in type 1 diabetes (T1D) by modulation of β-cell gene expression networks. The transcription factor Activator Protein-1 (AP-1) is a key regulator of inflammation and apoptosis. We presently evaluated the function of the AP-1 subunit JunB in cytokine-mediated β-cell dysfunction and death. The cytokines IL-1β+IFN-γ induced an early and transitory upregulation of JunB by NF-κB activation. Knockdown of JunB by RNA interference increased cytokine-mediated expression of inducible nitric oxide synthase (iNOS) and endoplasmic reticulum (ER) stress markers, leading to increased apoptosis in an insulin-producing cell line (INS-1E) and in purified rat primary β-cells. JunB knockdown β-cells and junB−/− fibroblasts were also more sensitive to the chemical ER stressor cyclopiazonic acid (CPA). Conversely, adenoviral-mediated overexpression of JunB diminished iNOS and ER markers expression and protected β-cells from cytokine-induced cell death. These findings demonstrate a novel and unexpected role for JunB as a regulator of defense mechanisms against cytokine- and ER stress-mediated apoptosis

JNK3 Maintains Expression of the Insulin Receptor Substrate 2 (IRS2) in Insulin-Secreting Cells: Functional Consequences for Insulin Signaling

We have recently shown that silencing of the brain/islet specific c-Jun N-terminal Kinase3 (JNK3) isoform enhances both basal and cytokine-induced beta-cell apoptosis, whereas silencing of JNK1 or JNK2 has opposite effects. While it is known that JNK1 or JNK2 may promote apoptosis by inhibiting the activity of the pro-survival Akt pathway, the effect of JNK3 on Akt has not been documented. This study aims to determine the involvement of individual JNKs and specifically JNK3 in the regulation of the Akt signaling pathway in insulin-secreting cells. JNK3 silencing strongly decreases Insulin Receptor Substrate 2 (IRS2) protein expression, and blocks Akt2 but not Akt1 activation by insulin, while the silencing of JNK1 or JNK2 activates both Akt1 and Akt2. Concomitantly, the silencing of JNK1 or JNK2, but not of JNK3, potently phosphorylates the glycogen synthase kinase3 (GSK3β). JNK3 silencing also decreases the activity of the transcription factor Forkhead BoxO3A (FoxO3A) that is known to control IRS2 expression, in addition to increasing c-Jun levels that are known to inhibit insulin gene expression. In conclusion, we propose that JNK1/2 on one hand and JNK3 on the other hand, have opposite effects on insulin-signaling in insulin-secreting cells; JNK3 protects beta-cells from apoptosis and dysfunction mainly through maintenance of a normal IRS2 to Akt2 signaling pathway. It seems that JNK3 mediates its effects mainly at the transcriptional level, while JNK1 or JNK2 appear to mediate their pro-apoptotic effect in the cytoplasm