Modulation of cardiomyocyte electrical properties using regulated bone morphogenetic protein-2 expression

Because cardiomyocytes lose their ability to divide after birth, any subsequent cell loss or dysfunction results in pathologic cardiac rhythm initiation or impulse conduction. Strategies to restore and control the electrophysiological activity of the heart may, therefore, greatly affect the regeneration of cardiac tissue functionality. Using lentivirus-derived particles to regulate the bone morphogenetic protein-2 (BMP-2) gene expression in a pristinamycin- or gaseous acetaldehyde-inducible manner, we demonstrated the adjustment of cardiomyocyte electrophysiological characteristics. Complementary metal oxide semiconductor-based high-density microelectrode arrays (HD-MEAs) were used to monitor the electrophysiological activity of neonatal rat cardiomyocytes (NRCs) cultured as monolayers (NRCml) or as microtissues (NRCmt). NRCmt more closely resembled heart tissue physiology than did NRCml and could be conveniently monitored using HD-MEAs because of their ability to detect low-signal events and to sub-select the region of interest, namely, areas where the microtissues were placed. Cardiomyocyte-forming microtissues, transduced using lentiviral vectors encoding BMP-2, were capable of restoring myocardial microtissue electrical activity. We also engineered NRCmt to functionally couple within a cardiomyocyte monolayer, thus showing pacemaker-like activity upon local regulation of transgenic BMP-2 expression. The controlled expression of therapeutic transgenes represents a crucial advance for clinical interventions and gene-function analysis.     

Ectopic expression of delta FBJ murine osteosarcoma viral oncogene homolog B mediates transdifferentiation of adipose-like spheroids into osteo-like microtissues

Differentiation and transdifferentiation strategies have a large role in the manipulation of cells in replacing dysfunctional cells and tissues. We developed adipose-like microtissues using gravity-enforced self-assembly of monodispersed human primary preadipocytes to determine their transdifferentiation capacity to form bone-like tissues. Using lentivirus-derived particles to induce ectopic bone morphogenetic protein (BMP)-2 and delta FBJ murine osteosarcoma viral oncogene homolog B (DeltaFosB) gene expression, we demonstrated a time-dependent induction of osteoblast-specific genes and properties such as calcium deposits, bone-like extracellular matrix (ECM), and matrix mineralization. DeltaFosB was able to trigger partial Pref-1-mediated de-differentiation of adipocytes, which also retained their adipocytic cell phenotype. Osteoblast-specific structures could be co-localized in the ECM of lipid-containing cells analyzed using immunofluorescence and transmission electron microscopy when BMP-2 and DeltaFosB were co-expressed, suggesting that differentiated adipocytes are able to transdifferentiate into osteoblasts via a transient hybrid adipocyte-preadipocyte-osteoblast cell phenotype. Microtissues transgenic for BMP-2 and DeltaFosB expression were able to reproduce bone matrix, which occurs to a lesser extent in conventional two-dimensional (2D) cultures but is known to play a decisive role in the development and function of bone in vivo. This demonstrates that ECM-inclusive studies are essential for future characterization assays. Therefore, 3D cultures provide a superior ex vivo system for the improved characterization of phenotypical and functional alterations resulting from interventions directed toward differentiation processes. Precise control of transdifferentiation of adipocytes into osteoblasts in a 3D culture mimicking in vivo tissue conditions as closely as possible will foster important advances in regenerative medicine and tissue engineering.     

Salivary protein profiles distinguish triatomine species and populations of Triatoma dimidiata (Hemiptera: Reduviidae)

Seven Triatoma dimidiata (Latreille, 1811) populations from different provinces of Guatemala were compared along with three related triatomine species using the electrophoretic profiles of salivary proteins. The analysis of salivary proteins allowed the separation of two of the species into their respective complexes, phyllosoma (T. pallidipennis) and protracta (T. nitida) (Lent and Wygodzinsky, 1979), whereas T. dimidiata seems slightly separated from either of these. Based on salivary protein profiles, T. dimidiata is most closely related to the cluster including T ryckmani and T. nitida (protracta) and more diverged from T. pallidipennis (phyllosoma). Among Guatemalan T. dimidiata populations, the cave population from Lanquin is separated from the rest of populations analyzed, suggesting that it is in the process of speciation. No difference in protein banding pattern was observed among populations from domestic and peridomestic ecotopes from the same region.     

Quality of life among caregivers of patients with eating disorders

Purpose  

To analyse health-related quality of life (HRQoL) and its associated social and clinical variables among a sample of caregivers of patients with eating disorders (ED).     

Tratamiento de la hemorragia uterina posparto mediante taponamiento mecánico con balón intrauterino

Objective

To demonstrate the usefulness of uterine balloon tamponade in postpartum hemorrhage.

Material and methods

Five term pregnancies with postpartum hemorrhage were studied. The criterion for balloon placement was persistent bleeding despite pharmacological treatment.

Results

Balloon placement was successful in 100% of the patients. The mean decrease in hemoglobin was 3.2 g/dl (range: 1-5) and an average of three units of packed red blood cells per patient were required (range: 0-6). The mean volume of saline solution per balloon was 312 ml (range: 160-420) and the mean duration of treatment was 22 hours (range: 12-30).

Conclusions

Uterine balloon tamponade is an efficient method to control postpartum hemorrhage. Training is not required for the application of this technique, which can obviate the need for surgery. Because of its ease of use and reasonable cost, this method can be used in any hospital setting.     

Repolarization of tumor infiltrating macrophages and increased survival in mouse primary CNS lymphomas after XPO1 and BTK inhibition

Journal of Neuro-Oncology - Patients diagnosed with primary central nervous system lymphoma (PCNSL) often face dismal outcomes due to the limited availability of therapeutic options. PCNSL cells...     

Allosteric enhancers for A1 adenosine receptor

Allosteric enhancers at the adenosine A(1) receptor have received attention as anti-arrhythmic cardiac agents, and, more recently, as anti-lipolytic agents. In addition, allosteric modulators at the adenosine A(1) receptor have therapeutic potential as analgesics and neuroprotective agents. In particular, the compounds with improved potency as enhancers and reduced antagonist properties are mentioned.     

Efficacy and safety of Vismodegib treatment in patients with advanced basal cell carcinoma and multiple comorbidities

Basal cell carcinoma (BCC) is the most common malignancy in Caucasians, and its incidence is increasing. Most BCCs are treated surgically, nevertheless surgery is not an effective treatment for locally advanced or metastatic BCC. Alterations in hedgehog signaling pathway, a key regulator of cell growth and differentiation during development, are implicated in the pathogenesis of basal‐cell carcinoma. Vismodegib is a small‐molecule inhibitor of smoothened (SMO), a key component of the hedgehog (Hh) signaling pathway, administered in BCC patients, especially when surgery and radiotherapy treatments have failed. We report a series of eight elderly patients treated with vismodegib for advanced BCC and affected by concomitant multiple comorbidities. The efficacy and tolerability of vismodegib in patients with single and/or multiple comorbidities has been poorly studied. In our observation an overall high safety and tolerability has been observed over the course of treatment, with side effects of grade I and II and no changes in vital parameters, electrocardiography and echocardiogram. Vismodegib has been shown to be a safe and well tolerated treatment option for elderly patients affected by multiple comorbidities and advanced BCC.