How Hypertension Affects Heart Metabolism

Hypertension is one of the most frequently observed cardiovascular diseases, which precedes heart failure in 75% of its cases. It is well-established that hypertensive patients have whole body metabolic complications such as hyperlipidemia, hyperglycemia, decreased insulin sensitivity or diabetes mellitus. Since myocardial metabolism is strictly dependent on hormonal status as well as substrate milieu, the above mentioned disturbances may affect energy generation status in the heart. Interestingly, it was found that hypertension induces a shift in substrate preference toward increased glucose utilization in cardiac muscle, prior to structural changes development. The present work reports advances in the aspect of heart metabolism under high blood pressure conditions, including human and the most common animal models of hypertension

Spatial Orientation in Japanese Quails (Coturnix coturnix japonica)

Finding a given location can be based on a variety of strategies, for example on the estimation of spatial relations between landmarks, called spatial orientation. In galliform birds, spatial orientation has been demonstrated convincingly in very young domestic chicks. We wanted to know whether adult Japanese quails (Coturnix coturnix japonica) without food deprivation are also able to use spatial orientation. The quails had to learn the relation of a food location with four conspicuous landmarks which were placed in the corners of a square shaped arena. They were trained to find mealworms in three adjacent food cups in a circle of 20 such cups. The rewarded feeders were located during training between the same two landmarks each of which showed a distinct pattern. When the birds had learned the task, all landmarks were displaced clockwise by 90 degrees. When tested in the new situation, all birds redirected their choices with respect to the landmark shift. In subsequent tests, however, the previously correct position was also chosen. According to our results, quails are using conspicuous landmarks as a first choice for orientation. The orientation towards the previously rewarded location, however, indicates that the neuronal representation of space which is used by the birds also includes more fine grain, less conspicuous cues, which are probably also taken into account in uncertain situations. We also presume that the rare orientation towards never rewarded feeders may be due to a foraging strategy instead of being mistakes

Neutrophils in Health and Disease: From Receptor Sensing to Inflammasome Activation

Neutrophils—polymorphonuclear cells (PMNs) are the cells of the initial immune response and make up the majority of leukocytes in the peripheral blood. After activation, these cells modify their functional status to meet the needs at the site of action or according to the agent causing injury. They receive signals from their surroundings and “plan” the course of the response in both temporal and spatial contexts. PMNs dispose of intracellular signaling pathways that allow them to perform a wide range of functions associated with the development of inflammatory processes. In addition to these cells, some protein complexes, known as inflammasomes, also have a special role in the development and maintenance of inflammation. These complexes participate in the proteolytic activation of key pro-inflammatory cytokines, such as IL-1β and IL-18. In recent years, there has been significant progress in the understanding of the structure and molecular mechanisms behind the activation of inflammasomes and their participation in the pathogenesis of numerous diseases. The available reports focus primarily on macrophages and dendritic cells. According to the literature, the activation of inflammasomes in neutrophils and the associated death type—pyroptosis—is regulated in a different manner than in other cells. The present work is a review of the latest reports concerning the course of inflammasome activation and inflammatory cytokine secretion in response to pathogens in neutrophils, as well as the role of these mechanisms in the pathogenesis of selected diseases

Autoimmunologiczny zespół insulinowy – opis przypadku

Not required for Clinical Vignette.Autoimmunologiczny zespół insulinowy to rzadka choroba, która najpowszechniej występuje w populacji azjatyckiej, natomiast poza nią jest spotykana incydentalnie. U jej podłoża leży obecność przeciwciał skierowanych przeciwko endogennej insulinie, tworząc kompleksy i ograniczając jej biologiczne działanie, co w konsekwencji powoduje nadmierne wydzielanie tego hormonu. Co więcej, rozpad kompleksów insulina-przeciwciała prowadzi do uwolnienia bioaktywnej insuliny – co w konsekwencji, klinicznie objawia się hipoglikemią. W artykule opisano przypadek 45-letniej kobiety polskiego pochodzenia, z objawami hipoglikemii od 3 miesięcy, ambulatoryjnie stwierdzanymi stężeniami insuliny przekraczającymi wartość 1000 μIU/ml oraz, pierwotnie, podejrzeniem insulinoma. Badanie tomografii komputerowej jamy brzusznej nie wykazało odchyleń. W toku diagnostyki wykonano 72-godzinny test głodowy i w zakresie stosunku stężeń insuliny do C-peptydu odnotowano cechy typowe dla autoimmunologicznego zespołu insulinowego. Diagnozę potwierdzono w teście precypitacji z 12,5% glikolem polietylenowym. Ze względu na rzadkie występowanie i podobieństwo obrazu klinicznego do innych hipoglikemii hiperinsulinemicznych autoimmunologiczny zespół insulinowy stwarza poważne trudności diagnostyczne. Niemniej, właściwe rozpoznanie jest niezmiernie ważne, gdyż w przeciwnym razie pacjent może być poddany niepotrzebnym, inwazyjnym zabiegom, jak w przypadkach guza insulinowego czy nesidioblastozy

Plasmid Mediated mcr-1.1 Colistin-Resistance in Clinical Extraintestinal Escherichia coli Strains Isolated in Poland

Objectives: The growing incidence of multidrug-resistant (MDR) bacteria is an inexorable and fatal challenge in modern medicine. Colistin is a cationic polypeptide considered a “last-resort” antimicrobial for treating infections caused by MDR Gram-negative bacterial pathogens. Plasmid-borne mcr colistin resistance emerged recently, and could potentially lead to essentially untreatable infections, particularly in hospital and veterinary (livestock farming) settings. In this study, we sought to establish the molecular basis of colistin-resistance in six extraintestinal Escherichia coli strains. Methods: Molecular investigation of colistin-resistance was performed in six extraintestinal E. coli strains isolated from patients hospitalized in Medical University Hospital, Bialystok, Poland. Complete structures of bacterial chromosomes and plasmids were recovered with use of both short- and long-read sequencing technologies and Unicycler hybrid assembly. Moreover, an electrotransformation assay was performed in order to confirm IncX4 plasmid influence on colistin-resistance phenotype in clinical E. coli strains. Results: Here we report on the emergence of six mcr-1.1-producing extraintestinal E. coli isolates with a number of virulence factors. Mobile pEtN transferase-encoding gene, mcr-1.1, has been proved to be encoded within a type IV secretion system (T4SS)-containing 33.3 kbp IncX4 plasmid pMUB-MCR, next to the PAP2-like membrane-associated lipid phosphatase gene. Conclusion: IncX4 mcr-containing plasmids are reported as increasingly disseminated among E. coli isolates, making it an “epidemic” plasmid, responsible for (i) dissemination of colistin-resistance determinants between different E. coli clones, and (ii) circulation between environmental, industrial, and clinical settings. Great effort needs to be taken to avoid further dissemination of plasmid-mediated colistin resistance among clinically relevant Gram-negative bacterial pathogens