Estatinas y factor de necrosis tumoral alfa

Las Estatinas son elaboradas para eliminar el riesgo cardiovascular al reducir LDL (colesterol de baja densidad), pero el evento coronario agudo sigue ocurriendo en 40% de las personas que presentaban colesterol total por debajo de lo normal. El objetivo de este estudio fue evaluar si dentro de los efectos pleiotropicos de las estatinas se podía reducir el FNTα y con ello probar sus efectos antioxidantes e inflamatorios. Se evaluaron 21 pacientes, con hipercolesterolemia al ingreso y después de 8 semanas de recibir 40 mg de Simvastatina, se le realizó: Colesterol, Triglicéridos, HDL, LDL, Glicemia, Creatinina, Acido Úrico, PCR, IL-1, IL-6, IL-10, TNFα, SOD y 8-Isoprostanos F2. Se utilizo la prueba t de student. La estatina, mas allá de disminuir LDL es eficaz en disminuir variables que participan en la respuesta oxidativa e inflamatoria, mecanismo fisiopatologico constantes en las enfermedades cardiovasculares y metabólicas.Statins are developed to eliminate the risk of heart disease by reducing LDL (low density), but the acute coronary event still happened in 40% of those who had total cholesterol below normal. The aim of this study was to assess whether in the pleiotropic effects of statins could reduce TNF α and thus prove its antioxidant and inflammatory effects. We evaluated 21 patients with hypercholesterolemia on admission and after 8 weeks of receiving 40 mg simvastatin, we evaluated: Cholesterol, Triglycerides, HDL, LDL, Glucose, Creatinine, uric acid, CRP, IL-1, IL-6, IL-10, TNF, SOD and 8-isoprostane F2α. T test was used to student. The statin beyond to reduced LDL is effective in decreasing variables involved in the inflammatory response, consistent pathophysiological mechanism in cardiovascular and metabolic diseases

Langtidsovervåking av miljøkvaliteten i kystområdene av Norge. Kystovervåkingsprogrammet. Årsrapport for 2009

Sammendrag Rapporten beskriver miljøkvaliteten i kystområdene av Sør-Norge i 2009, med spesiell fokus på tilstand og utvikling i næringssalttilførsler, vannkvalitet og det biologiske mangfoldet i plankton-, bløt- og hardbunns­samfunn. NAO-indeksen for vinteren 2009 var negativ, på grunn av kaldt klima i februar. Eutrofiutviklingen har vært positiv de siste årene. Vannføringen i Glomma var noe større enn normalt i 2009, men tilførslene av næringsalter fra elver har gått noe ned. Vannkvaliteten i Skagerrak var i 2009 i klasse God eller Meget god med hensyn til N, P, siktdyp og klorofyll, unntatt i Ytre Oslofjord hvor hvor det ble registrert tot-P og siktdyp i klasse Mindre god. For hele perioden er det i Skagerrak en tendens til avtakende risiko for opp­blom­string av skadelige alger. Økende oksygenforbruk i Risørfjorden og avtagende oksygen­konsentrasjoner i kystvannet generelt, gjenspeiler økt organisk belastning langs kysten. I 2009 var siktdypet som gjennomsnittet for 1991-2005, men i februar var sikten dårligere langs Skagerrakkysten. Det kan skyldes våroppblomstringen og innstrømmende vann fra Kattegat. 2009 var det åttende året på rad med lav algemengde. En kraftig våroppblomstring kom i februar. Lite alger kan være årsaken til nedgang i biomassen av kopepoder. Det ble registrert flere sørlige arter i våre områder i 2009. Tilstanden for bunndyr, både på bløtbunn og hardbunn, var generelt god i 2009, men tilstanden for tare har vært dårligere de siste to år.Klima- og forurensningsdirektoratet (Klif

Mitochondrial targeting of recombinant RNAs modulates the level of a heteroplasmic mutation in human mitochondrial DNA associated with Kearns Sayre Syndrome

Mitochondrial mutations, an important cause of incurable human neuromuscular diseases, are mostly heteroplasmic: mutated mitochondrial DNA is present in cells simultaneously with wild-type genomes, the pathogenic threshold being generally >70% of mutant mtDNA. We studied whether heteroplasmy level could be decreased by specifically designed oligoribonucleotides, targeted into mitochondria by the pathway delivering RNA molecules in vivo. Using mitochondrially imported RNAs as vectors, we demonstrated that oligoribonucleotides complementary to mutant mtDNA region can specifically reduce the proportion of mtDNA bearing a large deletion associated with the Kearns Sayre Syndrome in cultured transmitochondrial cybrid cells. These findings may be relevant to developing of a new tool for therapy of mtDNA associated diseases

Integrative clustering reveals a novel split in the luminal A subtype of breast cancer with impact on outcome

Background: Breast cancer is a heterogeneous disease at the clinical and molecular level. In this study we integrate classifications extracted from five different molecular levels in order to identify integrated subtypes. Methods: Tumor tissue from 425 patients with primary breast cancer from the Oslo2 study was cut and blended, and divided into fractions for DNA, RNA and protein isolation and metabolomics, allowing the acquisition of representative and comparable molecular data. Patients were stratified into groups based on their tumor characteristics from five different molecular levels, using various clustering methods. Finally, all previously identified and newly determined subgroups were combined in a multilevel classification using a "cluster-of-clusters" approach with consensus clustering. Results: Based on DNA copy number data, tumors were categorized into three groups according to the complex arm aberration index. mRNA expression profiles divided tumors into five molecular subgroups according to PAM50 subtyping, and clustering based on microRNA expression revealed four subgroups. Reverse-phase protein array data divided tumors into five subgroups. Hierarchical clustering of tumor metabolic profiles revealed three clusters. Combining DNA copy number and mRNA expression classified tumors into seven clusters based on pathway activity levels, and tumors were classified into ten subtypes using integrative clustering. The final consensus clustering that incorporated all aforementioned subtypes revealed six major groups. Five corresponded well with the mRNA subtypes, while a sixth group resulted from a split of the luminal A subtype; these tumors belonged to distinct microRNA clusters. Gain-of-function studies using MCF-7 cells showed that microRNAs differentially expressed between the luminal A clusters were important for cancer cell survival. These microRNAs were used to validate the split in luminal A tumors in four independent breast cancer cohorts. In two cohorts the microRNAs divided tumors into subgroups with significantly different outcomes, and in another a trend was observed. Conclusions: The six integrated subtypes identified confirm the heterogeneity of breast cancer and show that finer subdivisions of subtypes are evident. Increasing knowledge of the heterogeneity of the luminal A subtype may add pivotal information to guide therapeutic choices, evidently bringing us closer to improved treatment for this largest subgroup of breast cancer.Peer reviewe

Skeletal Muscle Differentiation Evokes Endogenous XIAP to Restrict the Apoptotic Pathway

Myotube apoptosis occurs normally during muscle development and aging but it can lead to destruction of skeletal muscle in neuromuscular diseases. Therefore, understanding how myotube apoptosis is regulated is important for developing novel strategies for treatment of muscle loss. We investigated the regulation of apoptosis in skeletal muscle and report a striking increase in resistance to apoptosis following differentiation. We find mitotic C2C12 cells (myoblast-like cells) are sensitive to cytosolic cytochrome c microinjection. However, differentiated C2C12 cells (myotube-like cells) and primary myotubes are markedly resistant. This resistance is due to endogenous X-linked inhibitor of apoptotic protein (XIAP). Importantly, the selective difference in the ability of XIAP to block myotube but not myoblast apoptosis is not due to a change in XIAP but rather a decrease in Apaf-1 expression. This decrease in Apaf-1 links XIAP to caspase activation and death. Our findings suggest that in order for myotubes to die, they may degrade XIAP, functionally inactivate XIAP or upregulate Apaf-1. Importantly, we identify a role for endogenous Smac in overcoming XIAP to allow myotube death. However, in postmitotic cardiomyocytes, where XIAP also restricts apoptosis, endogenous Smac was not capable of overcoming XIAP to cause death. These results show that as skeletal muscle differentiate, they become resistant to apoptosis because of the ability of XIAP to regulate caspase activation. The increased restriction of apoptosis in myotubes is presumably important to ensure the long term survival of these postmitotic cells as they play a vital role in the physiology of organisms

A mesenchymal to epithelial switch in Fgf10 expression specifies an evolutionary-conserved population of ionocytes in salivary glands

Fibroblast growth factor 10 (FGF10) is well established as a mesenchyme-derived growth factor and a critical regulator of fetal organ development in mice and humans. Using a single-cell RNA sequencing (RNA-seq) atlas of salivary gland (SG) and a tamoxifen inducible Fgf10CreERT2:R26-tdTomato mouse, we show that FGF10pos cells are exclusively mesenchymal until postnatal day 5 (P5) but, after P7, there is a switch in expression and only epithelial FGF10pos cells are observed after P15. Further RNA-seq analysis of sorted mesenchymal and epithelial FGF10pos cells shows that the epithelial FGF10pos population express the hall- marks of ancient ionocyte signature Forkhead box i1 and 2 (Foxi1, Foxi2), Achaete-scute homolog 3 (Ascl3), and the cystic fibrosis transmembrane conductance regulator (Cftr). We propose that epithelial FGF10pos cells are specialized SG ionocytes located in ducts and important for the ionic modification of saliva. In addition, they maintain FGF10-dependent gland homeostasis via communication with FGFR2bpos ductal and myoepithelial cells

Nature and frequency of respiratory involvement in chronic progressive external ophthalmoplegia

Chronic progressive external ophthalmoplegia (CPEO) is a relatively common mitochondrial disorder. Weakness of the extra-ocular, limb girdle and laryngeal muscles are established clinical features. Respiratory muscle involvement however has never been studied systematically, even though respiratory complications are one of the main causes of death. We therefore determined the prevalence and nature of respiratory muscle involvement in 23 patients with genetically confirmed CPEO. The main finding was decreased respiratory muscle strength, both expiratory (76.8% of predicted, p = 0.002) and inspiratory (79.5% of predicted, p = 0.004). Although the inspiratory vital capacity (92.5% of predicted, p = 0.021) and the forced expiratory volume in 1 s (89.3% of predicted, p = 0.002) were below predicted values, both were still within the normal range in the majority of patients. Expiratory weakness was associated with a decreased vital capacity (ρ = 0.502, p = 0.015) and decreased peak expiratory flow (ρ = 0.422, p = 0.045). Moreover, expiratory muscle strength was lower in patients with limb girdle weakness (62.6 ± 26.1% of predicted vs. 98.9 ± 22.5% in patients with normal limb girdle strength, p = 0.003), but was not associated with other clinical features, subjective respiratory complaints, disease severity or disease duration. Since respiratory involvement in CPEO is associated with severe morbidity and mortality, the present data justify periodic assessment of respiratory functions in all CPEO patients

Localization of AQP5 during development of the mouse submandibular salivary gland

Aquaporin 5 (AQP5) is known to be central for salivary fluid secretion. A study of the temporal-spatial distribution of AQP5 during submandibular gland (SMG) development and in adult tissues might offer further clues to its unknown role during development. In the present work, SMGs from embryonic day (E) 14.5–18.5 and postnatal days (P) 0, 2, 5, 25, and 60 were immunostained for AQP5 and analyzed using light microscopy. Additional confocal and transmission electron microscopy were performed on P60 glands. Our results show that AQP5 expression first occurs in a scattered pattern in the late canalicular stage and becomes more prominent and organized in the terminal tubuli/pro-acinar cells towards birth. Additional apical membrane staining in the entire intralobular duct is found just prior to birth. During postnatal development, AQP5 is expressed in both the luminal and lateral membrane of pro-acinar/acinar cells. AQP5 is also detected in the basal membrane of acinar cells at P25 and P60. In the intercalated ducts at P60, the male glands show apical staining in the entire segment, while only the proximal region is positive in the female glands. These results demonstrate an evolving distribution of AQP5 during pre- and postnatal development in the mouse SMGs