Pagalbinės kraujotakos taikymas gydant miokardito sukeltą kardiogeninį šoką

Background. Cardiogenic shock caries high mortality and morbidity. Myocarditis patients developing cardiogenic shock refractory to medical treatment might benefit from extracorporeal membrane oxygenation or mechanical ventricular assist devices. Methods. A retrospective, single center observational study to assess the rate and outcomes of mechanical circulatory support of patients with fulminant myocarditis related cardiogenic shock. Short-term outcomes were evaluated. The primary endpoint of the study was hospital survival. Results. Two hundred ninetyone patient were supported with short-term mechanical assist devices at our institution during 12 year period. Among them, 4 (1.4%) were treated for myocarditis related cardiogenic shock. All patients were female, with a mean age of 34±4 years. In one case surgically implantable short-term mechanical assist device was used, in other three cases – extracorporeal membrane oxygenation. The mean duration of the support was 364±273 hours, mean intensive care unit stay – 35±29 days. Three of four patients were successfully weaned from the support and discharged from the hospital with complete heart function recovery. Conclusion. Patient with fulminant myocarditis, who would have died without the initiation of mechanical circulatory, had favorable short-term outcome with 75% survival rate.Įvadas. Išsivysčius kardiogeniniam šokui, labai didelė mirštamumo ir komplikacijų rizika. Gydant miokardito sukeltą ūmų kardiogeninį šoką, gali būti veiksmingos mechaninės kraujotakos palaikymo priemonės. Tyrimo metodika. Atlikta miokardito sukelto kardiogeninio šoko atvejų, kai pacientų būklei stabilizuoti naudota pagalbinė kraujotaka, retrospektyvioji analizė. Tyrimo metu analizuoti šoko gydymo, naudojant pagalbinę kraujotaką, rezultatai. Studijos tikslas – įvertinti hospitalinį išgyvenamumą. Rezultatai. Tiriamuoju 12 m. laikotarpiu pagalbinė kraujotaka taikyta 291 pacientui. Iš jų tik 4 (1,4 %) pacientams buvo nustatytas miokardito sukeltas kardiogeninis šokas. Visos pacientės – jauno amžiaus moterys (amžiaus vidurkis – 33±4 m.). Vienu atveju naudota chirurgiškai implantuojama trumpalaikė kairįjį ir dešinįjį širdies skilvelius pavaduojanti kraujotaka, trimis atvejais – ekstrakorporinė membraninė oksigenacija (EKMO). Širdies veiklą pavaduojant mechaninei kraujotakai, vidutinė gydymo trukmė – 364±273 val., vidutinė gydymo intensyviosios terapijos skyriuje trukmė – 35±29 paros. Trims iš keturių pacienčių pagalbinė kraujotaka buvo sėkmingai atjungta, šios pacientės, atkūrus širdies kontraktilinę funkciją, išrašytos iš ligoninės. Išvados. Miokardito sąlygotas ūmus širdies nepakankamumas nėra dažna, tačiau labai grėsminga komplikacija. Mechaninės kraujotakos palaikymo priemonės leidžia pasiekti 75 proc. išgyvenamumą

Dimethylarginine Dimethylaminohydrolase II Overexpression Attenuates LPS-Mediated Lung Leak in Acute Lung Injury

Acute lung injury (ALI) is a severe hypoxemic respiratory insufficiency associated with lung leak, diffuse alveolar damage, inflammation, and loss of lung function. Decreased dimethylaminohydrolase (DDAH) activity and increases in asymmetric dimethylarginine (ADMA), together with exaggerated oxidative/nitrative stress, contributes to the development of ALI in mice exposed to LPS. Whether restoring DDAH function and suppressing ADMA levels can effectively ameliorate vascular hyperpermeability and lung injury in ALI is unknown, and was the focus of this study. In human lung microvascular endothelial cells, DDAH II overexpression prevented the LPS-dependent increase in ADMA, superoxide, peroxynitrite, and protein nitration. DDAH II also attenuated the endothelial barrier disruption associated with LPS exposure. Similarly, in vivo, we demonstrated that the targeted overexpression of DDAH II in the pulmonary vasculature significantly inhibited the accumulation of ADMA and the subsequent increase in oxidative/nitrative stress in the lungs of mice exposed to LPS. In addition, augmenting pulmonary DDAH II activity before LPS exposure reduced lung vascular leak and lung injury and restored lung function when DDAH activity was increased after injury. Together, these data suggest that enhancing DDAH II activity may prove a useful adjuvant therapy to treat patients with ALI

Selenium supplementation modulates apoptotic processes in thyroid follicular cells

Selenium (Se) is an essential micronutrient modulating several physiopathological processes in the human body. The aim of the study is to characterize the molecular effects determined by Se-supplementation in thyroid follicular cells, using as model the well-differentiated rat thyroid follicular cell line FRTL5. Experiments have been performed to evaluate the effects of Se on cell growth, mortality and proliferation and on modulation of pro- and antiapoptotic pathways. The results indicate that Se-supplementation improves FRTL5 growth rate. Furthermore, Se reduces the proportion of cell death and modulates both proapoptotic (p53 and Bim) and antiapoptotic (NF-kB and Bcl2) mRNA levels. In addition, incubation with high doses of Na-Se might prevent the ER-stress apoptosis induced by tunicamycin, as assessed by membrane integrity maintenance, reduction in caspase 3/7 activities, and reduction in Casp-3 and PARP cleavage. Taken together, these results provide molecular evidences indicating the role of Se supplementation on cell death and apoptosis modulation in thyroid follicular cells. These observations may be useful to understand the effects of this micronutrient on the physiopathology of the thyroid gland. © 2017 The Authors BioFactors published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology, 2017

Reciprocal regulation of the basic helix-loop-helix/Per-Arnt-Sim partner proteins, Arnt and Arnt2, during neuronal differentiation

Basic helix–loop–helix/Per–Arnt–Sim (bHLH/PAS) transcription factors function broadly in development, homeostasis and stress response. Active bHLH/PAS heterodimers consist of a ubiquitous signal-regulated subunit (e.g., hypoxia-inducible factors, HIF-1α/2α/3α; the aryl hydrocarbon receptor, AhR) or tissue-restricted subunit (e.g., NPAS1/3/4, Single Minded 1/2), paired with a general partner protein, aryl hydrocarbon receptor nuclear translocator (Arnt or Arnt2). We have investigated regulation of the neuron-enriched Arnt paralogue, Arnt2. We find high Arnt/Arnt2 ratios in P19 embryonic carcinoma cells and ES cells are dramatically reversed to high Arnt2/Arnt on neuronal differentiation. mRNA half-lives of Arnt and Arnt2 remain similar in both parent and neuronal differentiated cells. The GC-rich Arnt2 promoter, while heavily methylated in Arnt only expressing hepatoma cells, is methylation free in P19 and ES cells, where it is bivalent with respect to active H3K4me3 and repressive H3K27me3 histone marks. Typical of a ‘transcription poised’ developmental gene, H3K27me3 repressive marks are removed from Arnt2 during neuronal differentiation. Our data are consistent with a switch to predominant Arnt2 expression in neurons to allow specific functions of neuronal bHLH/PAS factors and/or to avoid neuronal bHLH/PAS factors from interfering with AhR/Arnt signalling.Nan Hao, Veronica L. D. Bhakti, Daniel J. Peet and Murray L. Whitela

Olfactory Receptors in Non-Chemosensory Organs: The Nervous System in Health and Disease

Olfactory receptors (ORs) and down-stream functional signaling molecules adenylyl cyclase 3 (AC3), olfactory G protein \u3b1 subunit (G\u3b1olf), OR transporters receptor transporter proteins 1 and 2 (RTP1 and RTP2), receptor expression enhancing protein 1 (REEP1), and UDP-glucuronosyltransferases (UGTs) are expressed in neurons of the human and murine central nervous system (CNS). In vitro studies have shown that these receptors react to external stimuli and therefore are equipped to be functional. However, ORs are not directly related to the detection of odors. Several molecules delivered from the blood, cerebrospinal fluid, neighboring local neurons and glial cells, distant cells through the extracellular space, and the cells' own self-regulating internal homeostasis can be postulated as possible ligands. Moreover, a single neuron outside the olfactory epithelium expresses more than one receptor, and the mechanism of transcriptional regulation may be different in olfactory epithelia and brain neurons. OR gene expression is altered in several neurodegenerative diseases including Parkinson's disease (PD), Alzheimer's disease (AD), progressive supranuclear palsy (PSP) and sporadic Creutzfeldt-Jakob disease (sCJD) subtypes MM1 and VV2 with disease-, region- and subtype-specific patterns. Altered gene expression is also observed in the prefrontal cortex in schizophrenia with a major but not total influence of chlorpromazine treatment. Preliminary parallel observations have also shown the presence of taste receptors (TASRs), mainly of the bitter taste family, in the mammalian brain, whose function is not related to taste. TASRs in brain are also abnormally regulated in neurodegenerative diseases. These seminal observations point to the need for further studies on ORs and TASRs chemoreceptors in the mammalian brain

La pénétration des aérosols médicamenteux dans les voies respiratoires, exemples d'application en station thermale

On connaît mieux, depuis quelques années, l'efficacité des mécanismes de dépôt des particules dans les voies respiratoires. Par ailleurs les progrès de la physique des aérosols nous ont donné les moyens de mesurer toutes sortes d'aérosols dont ceux utilisés en thérapeutique. La station thermale de LA BOURBOULE, qui utilise largement les aérosols d'eau thermale, profite de ces connaissances nouvelles pour standardiser ses pratiques à un niveau maximal de rendement pour le curiste moyen. Pour illustrer cette démarche, on expose d'abord les connaissances utilisables concernant le dépôt des particules médicamenteuses dans les voies respiratoires, puis on donne les caractéristiques des aérosols d'eau thermale de LA BOURBOULE, ce qui permet de calculer les doses moyennes de produit actif qui peuvent être fixées

Accompagner l’appropriation des TIC : repères et méthodologie

International audienc