Nuclear inositol 1,4,5-trisphosphate is a necessary and conserved signal for the induction of both pathological and physiological cardiomyocyte hypertrophy

It is well established that inositol 1,4,5-trisphosphate (IP3) dependent Ca(2+) signaling plays a crucial role in cardiomyocyte hypertrophy. However, it is not yet known whether nuclear IP3 represents a Ca(2+) mobilizing pathway involved in this process. The goal of the current work was to investigate the specific role of nuclear IP3 in cardiomyocyte hypertrophic response. In this work, we used an adenovirus construct that selectively buffers IP3 in the nuclear region of neonatal cardiomyocytes. We showed for the first time that nuclear IP3 mediates endothelin-1 (ET-1) induced hypertrophy. We also found that both calcineurin (Cn)/nuclear factor of activated T Cells (NFAT) and histone deacetylase-5 (HDAC5) pathways require nuclear IP3 to mediate pathological cardiomyocyte growth. Additionally, we found that nuclear IP3 buffering inhibited insulin-like growth factor-1 (IGF-1) induced hypertrophy and prevented reexpression of fetal gene program. Together, these results demonstrated that nuclear IP3 is an essential and a conserved signal for both pathological and physiological forms of cardiomyocyte hypertrophy.     

Muscle endothelial-dependent microvascular dysfunction in adulthood due to early postnatal overnutrition

The aims of our study were to investigate effects of postnatal overnutrition, obtained by restricting the number of pups per litter, on microcirculatory reactivity, fat depots, its total percentage and lipid profile. Microvascular reactivity was evaluated in the cremaster muscle of 24 hamsters divided into four groups, with 6 animals in each one: normal (NL) and restricted (RL) litter groups, both at 6th and 21st weeks of age. The NL group had 8-9 pups and the RL 3 pups per litter and to avoid the litter effect, only one animal was used per litter. The results have shown that the RL group had higher velocity of weight, body mass and fat gain compared to the NL one at weeks 6 and 21. Significant differences were also observed on urogenital fat depot, total cholesterol and low density lipoprotein between groups. At the lowest concentration of Ach, the RL group showed smaller arteriolar dilatation at the 21st than at the 6th week [5(3-13) vs 19(8-40)%, p<0.01] while the NL one did not show any difference within the group. The highest concentration of Ach at the 21th week pointed to endothelial-dependent microvascular dysfunction in RL compared to NL [3(8-26) vs. 13(8-26)%, p<0.05]. Endothelial-independent microvascular reactivity was similar between groups. Our data suggest that postnatal overnutrition is associated to muscle endothelial-dependent microvascular dysfunction, greater body mass and total percentage of fat and impaired the lipid profile. In conclusion, the imprinting promoted by this experimental model of obesity was able to influence microvascular reactivity later in life.     

Tongue retraining and occlusal stability in a young adult. Case report

The clinical observation describes the case of a 20-year-old woman who has consulted for aesthetic and functional reasons. She presents a skeletal class III normodivergent, an occlusal class III with a lower proalveoli quite marked. In addition, a lingual dysfunction which manifests itself by important anterior diastema and dento-dental disharmony at the upper jaw complicates the case. The undertaken therapeutic project starts with a first step of a lingual praxis rehabilitation, followed by an orthodontic step and upper lateral incisors-plasty. The purpose of those results is the evaluation of the stability two years later, which was reported positive.     

The interference of the cleaning procedure of root walls with two different solvents on the adhesion of fiberglass intraradicular posts

Aim: This study was undertaken to examine the effect of root canal (RT) sealers content and the cleaning procedure of RT walls on bond strength (BS) of a fiber reinforced composite (FRC) post cemented with resin-based or zinc phosphate cement. Materials and methods: Forty bovine roots were divided into 2 groups (n = 20) and obturated with gutta-percha points plus Sealer 26 sealer or gutta-percha points plus N-Rickert sealer. In each group, half (n = 10) of intracanal walls was cleaned with ethanol and the other half with sulfuric ether. In each of these subgroups, half of intracanal posts (n = 5) were cemented with Bistite resin-based cement and half with zinc phosphate cement. Specimens were submitted to pull-out test and tensile force until post dislodgement. The maximum forces required for post removal was expressed in MPa, means were submitted to statistical analysis (Analysis of Variance Test, a = 0.05). Results: Fiber reinforced composite cemented with zinc phosphate were significantly more retentive than those cemented with Bistite (p < 0.05). Regarding the influence of eugenol-based sealer on post retention, there was a statistically significant difference (p < 0.05) only between groups cemented with Bistite, in which canals filled with N-Rickert + gutta-percha showed lower BS than canals filled with Sealer 26 + gutta-percha. Conclusion: Despite endodontic cement used, higher pull-out bond strength were obtained when posts were cemented with zinc phosphate. Clinical significance: The importance of ethanol or sulphuric ether application to properly replace water from intraradicular dentine still requires further investigations, especially to clarify if this technique may reduce the effect of aging and improve the stability of the bond, when used to cement fiber posts into the root canal. Keywords: Laboratory research, Dentin, Eugenol, Resin cements, Root canal filling material, Pull-out test, Cleaning procedure. How to cite this article: Gomes MF, Botta SB, Matos AB, Garone- Netto N. The Interference of the Cleaning Procedure of Root Walls with Two Different Solvents on the Adhesion of Fiberglass Intraradicular Posts. J Contemp Dent Pract 2012;13(3):275-279. Source of support: Nil Conflict of interest: None declared.     

Distinct roles for long-term hematopoietic stem cells and erythroid precursor cells in a murine model of Jak2V617F-mediated polycythemia vera

In the current model of the pathogenesis of polycythemia vera (PV), the JAK2V617F mutation arises in hematopoietic stem cells (HSCs) that maintain the disease, while erythroid precursor populations expand, resulting in excessive red blood cell production. We examined the role of these specific cell populations using a conditional Jak2V617F knockin murine model. We demonstrate that the most immature long-term (LT) HSCs are solely responsible for initiating and maintaining the disease in vivo and that Jak2V617F mutant LT-HSCs dominate hematopoiesis over time. When we induced Jak2V617F expression in erythropoietin receptor expressing precursor cells, the mice developed elevated hematocrit, expanded erythroid precursors, and suppressed erythropoietin levels. However, the disease phenotype was significantly attenuated compared with mice expressing Jak2V617F in LT-HSCs. In addition to developing a PV phenotype, all mice transplanted with Jak2V617F LT-HSCs underwent myelofibrotic transformation over time. These findings recapitulate the development of post-PV myelofibrosis in human myeloproliferative neoplasms. In aggregate, these results demonstrate the distinct roles of LT-HSCs and erythroid precursors in the pathogenesis of PV.     

A novel method of surgical site infection surveillance after cardiac surgery by active participation of stake holders

We describe a comprehensive surveillance system involving infection control practitioners, surgeons, administrative staff, and patients aimed at improving the postdischarge surveillance of surgical site infections. The system was able to detect 22 infections out of 538 procedures, 95% of which were detected during the postdischarge period.     

Receptor Trafficking and the Regulation of Synaptic Plasticity by SUMO

Timely and efficient information transfer at synapses is fundamental to brain function. Synapses are highly dynamic structures that exhibit long-lasting activity-dependent alterations to their structure and transmission efficiency, a phenomenon termed synaptic plasticity. These changes, which occur through alterations in presynaptic release or in the trafficking of postsynaptic receptor proteins, underpin the formation and stabilisation of neural circuits during brain development, and encode, process and store information essential for learning, memory and cognition. In recent years, it has emerged that the ubiquitin-like posttranslational modification SUMOylation is an important mediator of several aspects of neuronal and synaptic function. Through orchestrating synapse formation, presynaptic release and the trafficking of postsynaptic receptor proteins during forms of synaptic plasticity such as long-term potentiation, long-term depression and homeostatic scaling, SUMOylation is being increasingly appreciated to play a central role in neurotransmission. In this review, we outline key discoveries in this relatively new field, provide an update on recent progress regarding the targets and consequences of protein SUMOylation in synaptic function and plasticity, and highlight key outstanding questions regarding the roles of protein SUMOylation in the brain.