Manejo quirúrgico de frenillo superior: reporte de caso

Usualmente se observa frenillos patológicos en diversos pacientes de grupos de edades distintos. La presencia de estos frenillos con una inserción inadecuada  van ha conllevar principalmente a problemas fonéticos; así como también estéticos; compromiso en la oclusión, razón por la cual es sumamente importante valorar la historia clínica del paciente para  su manejo clínico-quirúrgico adecuado a aplicar según la elección del profesional luego de la valoración de la historia clínica.Se reporta un caso clínico de un paciente de sexo masculino de 7 años de edad, que asiste a consulta con su apoderado, manifestando “problemas al hablar”. Se realizó  frenectomía superior con la finalidad de corregir el frenillo patológico. Realizamos controles post operatorio los cuales finalizaron en resultados estéticos y funcionales satisfactorios para el paciente

Towards automated composition of convergent services: A survey

A convergent service is defined as a service that exploits the convergence of communication networks and at the same time takes advantage of features of the Web. Nowadays, building up a convergent service is not trivial, because although there are significant approaches that aim to automate the service composition at different levels in the Web and Telecom domains, selecting the most appropriate approach for specific case studies is complex due to the big amount of involved information and the lack of technical considerations. Thus, in this paper, we identify the relevant phases for convergent service composition and explore the existing approaches and their associated technologies for automating each phase. For each technology, the maturity and results are analysed, as well as the elements that must be considered prior to their application in real scenarios. Furthermore, we provide research directions related to the convergent service composition phases

Homeostatic control of polyamine levels under long-term salt stress in Arabidopsis

Salt stress has been frequently studied in its first osmotic phase. Very often, data regarding the second ionic phase is missing. It has also been suggested that Putrescine or/and Spermine could be responsible for salt resistance. In order to test this hypothesis under long-term salt stress, we obtained Arabidopsis thaliana transgenic plants harboring pRD29A::oatADC or pRD29A::GUS construction. Although Putrescine was the only polyamine significantly increased after salt acclimation in pRD29A::oatADC transgenic lines, this rendered in no advantage to this kind of stress. The higher Spermine levels found in WT and transgenic lines when compared to control conditions along with no increment on Putrescine levels in WT plants under salt acclimation, leads us to analyze Spermine effect on pADC1 and pADC2 expression. Increasing levels of this polyamine inhibits these promoters expression while enhances pRD29A expression, making Spermine the polyamine responsible for salt acclimation, and the transgenic lines developed in this work suitable for studying Putrescine roles in conditions where its biosynthesis would be inhibited in the WT genotype

Concentration-Dependency and Time Profile of Insulin Secretion: Dynamic Perifusion Studies With Human and Murine Islets

The detailed characterization and quantification of the kinetics of glucose-stimulated insulin secretion (GSIS) by normal pancreatic islets is of considerable interest for characterizing β-cell dysfunction, assessing the quality of isolated islets, and improving the design of artificial pancreas devices. Here, we performed dynamic evaluation of GSIS by human and mouse islets at high temporal resolution (every minute) in response to different glucose steps using an automated multichannel perifusion instrument. In both species, insulin responses were biphasic (a transient first-phase peak followed by a sustained second-phase), and the amount of insulin released showed a sigmoid-type dependence on glucose concentration. However, compared to murine islets, human islets have (1) a less pronounced first-phase response, (2) a flat secretion rate during second-phase response, (3) a left-shifted concentration response (reaching half-maximal response at 7.9 ± 0.4 vs. 13.7 ± 0.6 mM), and (4) an ~3-fold lower maximal secretion rate (8.3 ± 2.3 vs. 23.9 ± 5.1 pg/min/islet at 30 mM glucose). These results can be used to establish a more informative protocol for the calculation of the stimulation index, which is widely used for islet assessment in both research and clinical applications, but without an accepted standard or clear evidence as to what low- to high-glucose steps can provide better characterization of islet function. Data obtained here suggest that human islet functionality might be best characterized with a dynamic stimulation index obtained with a glucose step from a low of 4-5 to a high of 14-17 mM (e.g., G4 → G16)

Methylene Blue Inhibits the SARS-CoV-2 Spike-ACE2 Protein-Protein Interaction-a Mechanism that can Contribute to its Antiviral Activity Against COVID-19

Due to our interest in the chemical space of organic dyes to identify potential small-molecule inhibitors (SMIs) for protein-protein interactions (PPIs), we initiated a screen of such compounds to assess their inhibitory activity against the interaction between SARS-CoV-2 spike protein and its cognate receptor ACE2, which is the first critical step initiating the viral attachment and entry of this coronavirus responsible for the ongoing COVID-19 pandemic. As part of this, we found that methylene blue, a tricyclic phenothiazine compound approved by the FDA for the treatment of methemoglobinemia and used for other medical applications (including the inactivation of viruses in blood products prior to transfusion when activated by light), inhibits this interaction. We confirmed that it does so in a concentration-dependent manner with a low micromolar half-maximal inhibitory concentration (IC = 3 μM) in our protein-based ELISA-type setup, while chloroquine, siramesine, and suramin showed no inhibitory activity in this assay. Erythrosine B, which we have shown before to be a promiscuous SMI of PPIs, also inhibited this interaction. Methylene blue inhibited the entry of a SARS-CoV-2 spike bearing pseudovirus into ACE2-expressing cells with similar IC (3.5 μM). Hence, this PPI inhibitory activity could contribute to its antiviral activity against SARS-CoV-2 even in the absence of light by blocking its attachment to ACE2-expressing cells and making this inexpensive and widely available drug potentially useful in the prevention and treatment of COVID-19 as an oral or inhaled medication

Design, Synthesis, and Evaluation of Novel Immunomodulatory Small Molecules Targeting the CD40–CD154 Costimulatory Protein-Protein Interaction

We report the design, synthesis, and testing of novel small-molecule compounds targeting the CD40–CD154 (CD40L) costimulatory interaction for immunomodulatory purposes. This protein-protein interaction (PPI) is a TNF-superfamily (TNFSF) costimulatory interaction that is an important therapeutic target since it plays crucial roles in the activation of T cell responses, and there is resurgent interest in its modulation with several biologics in development. However, this interaction, just as all other PPIs, is difficult to target by small molecules. Following up on our previous work, we have now identified novel compounds such as DRI-C21091 or DRI-C21095 that show activity (IC50) in the high nanomolar to low micromolar range in the binding inhibition assay and more than thirty-fold selectivity versus other TNFSF PPIs including OX40–OX40L, BAFFR-BAFF, and TNF-R1-TNFα. Protein thermal shift (differential scanning fluorimetry) assays indicate CD154 and not CD40 as the binding partner. Activity has also been confirmed in cell assays and in a mouse model (alloantigen-induced T cell expansion in a draining lymph node). Our results expand the chemical space of identified small-molecule CD40–CD154 costimulatory inhibitors and provide lead structures that have the potential to be developed as orally bioavailable immunomodulatory therapeutics that are safer and less immunogenic than corresponding biologics

Small-Molecule In Vitro Inhibitors of the Coronavirus Spike – ACE2 Protein-Protein Interaction as Blockers of Viral Attachment and Entry for SARS-CoV-2

ABSTRACT Inhibitors of the protein-protein interaction (PPI) between the SARS-CoV-2 spike protein and ACE2, which acts as a ligand-receptor pair that initiates the viral attachment and cellular entry of this coronavirus causing the ongoing COVID-19 pandemic, are of considerable interest as potential antiviral agents. While blockade of such PPIs with small molecules is more challenging than with antibodies, small-molecule inhibitors (SMIs) might offer alternatives that are less strain- and mutation-sensitive, suitable for oral or inhaled administration, and more controllable / less immunogenic. Here, we report the identification of SMIs of this PPI by screening our compound-library that is focused on the chemical space of organic dyes. Among promising candidates identified, several dyes (Congo red, direct violet 1, Evans blue) and novel drug-like compounds (DRI-C23041, DRI-C91005) inhibited the interaction of hACE2 with the spike proteins of SARS-CoV-2 as well as SARS-CoV with low micromolar activity in our cell-free ELISA-type assays (IC50s of 0.2-3.0 μM); whereas, control compounds, such as sunset yellow FCF, chloroquine, and suramin, showed no activity. Protein thermal shift assays indicated that the SMIs identified here bind SARS-CoV-2-S and not ACE2. Selected promising compounds inhibited the entry of a SARS-CoV-2-S expressing pseudovirus into ACE2-expressing cells in concentration-dependent manner with low micromolar IC50s (6-30 μM). This provides proof-of-principle evidence for the feasibility of small-molecule inhibition of PPIs critical for coronavirus attachment/entry and serves as a first guide in the search for SMI-based alternative antiviral therapies for the prevention and treatment of diseases caused by coronaviruses in general and COVID-19 in particular. Competing Interest Statement The University of Miami has filed a patent on these compounds and their use for this application with P.B. as inventor. All other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. * ABBREVIATIONS ACE2 angiotensin converting enzyme 2 CoV coronavirus PPI protein-protein interaction SARS severe acute respiratory syndrome SMI small-molecule inhibito