Enhanced pharmacological efficacy of sumatriptan due to modification of its physicochemical properties by inclusion in selected cyclodextrins

The study focused on the pharmacological action of sumatriptan, in particular its antiallodynic and antihyperalgesic properties, as an effect of cyclodextrinic inclusion of sumatriptan, resulting in changes of its physicochemical qualities such as dissolution and permeability through artificial biological membranes, which had previously been examined in vitro in a gastro-intestinal model. The inclusion of sumatriptan into β-cyclodextrin and 2-hydroxylpropylo-β-cyclodextrin by kneading was confirmed with the use of spectral (fourier-transform infrared spectroscopy (FT-IR); solid state nuclear magnetic resonance spectroscopy with magic angle spinning condition, 1H and 13C MAS NMR) and thermal (differential scanning calorimetry (DSC)) methods. A precise indication of the domains of sumatriptan responsible for its interaction with cyclodextrin cavities was possible due to a theoretical approach to the analysis of experimental spectra. A high-performance liquid chromatography with a diode-array detector method (HPLC-DAD) was employed to determine changes in the concentration of sumatriptan during dissolution and permeability experiments. The inclusion of sumatriptan in complex with cyclodextrins was found to significantly modify its dissolution profiles by increasing the concentration of sumatriptan in complexed form in an acceptor solution compared to in its free form. Following complexation, sumatriptan manifested an enhanced ability to permeate through artificial biological membranes in a gastro-intestinal model for both cyclodextrins at all pH values. As a consequence of the greater permeability of sumatriptan and its increased dissolution from the complexes, an improved pharmacological response was observed when cyclodextrin complexes were applied

Supplement: "Localization and broadband follow-up of the gravitational-wave transient GW150914" (2016, ApJL, 826, L13)

This Supplement provides supporting material for Abbott et al. (2016a). We briefly summarize past electromagnetic (EM) follow-up efforts as well as the organization and policy of the current EM follow-up program. We compare the four probability sky maps produced for the gravitational-wave transient GW150914, and provide additional details of the EM follow-up observations that were performed in the different bands

Type 2 Diabetes Variants Disrupt Function of SLC16A11 through Two Distinct Mechanisms

Type 2 diabetes (T2D) affects Latinos at twice the rate seen in populations of European descent. We recently identified a risk haplotype spanning SLC16A11 that explains ∼20% of the increased T2D prevalence in Mexico. Here, through genetic fine-mapping, we define a set of tightly linked variants likely to contain the causal allele(s). We show that variants on the T2D-associated haplotype have two distinct effects: (1) decreasing SLC16A11 expression in liver and (2) disrupting a key interaction with basigin, thereby reducing cell-surface localization. Both independent mechanisms reduce SLC16A11 function and suggest SLC16A11 is the causal gene at this locus. To gain insight into how SLC16A11 disruption impacts T2D risk, we demonstrate that SLC16A11 is a proton-coupled monocarboxylate transporter and that genetic perturbation of SLC16A11 induces changes in fatty acid and lipid metabolism that are associated with increased T2D risk. Our findings suggest that increasing SLC16A11 function could be therapeutically beneficial for T2D. Video Abstract [Figure presented] Keywords: type 2 diabetes (T2D); genetics; disease mechanism; SLC16A11; MCT11; solute carrier (SLC); monocarboxylates; fatty acid metabolism; lipid metabolism; precision medicin

Localization and Broadband Follow-up of the Gravitational-wave Transient GW150914

A gravitational-wave (GW) transient was identified in data recorded by the Advanced Laser Interferometer Gravitational-wave Observatory (LIGO) detectors on 2015 September 14. The event, initially designated G184098 and later given the name GW150914, is described in detail elsewhere. By prior arrangement, preliminary estimates of the time, significance, and sky location of the event were shared with 63 teams of observers covering radio, optical, near-infrared, X-ray, and gamma-ray wavelengths with ground- and space-based facilities. In this Letter we describe the low-latency analysis of the GW data and present the sky localization of the first observed compact binary merger. We summarize the follow-up observations reported by 25 teams via private Gamma-ray Coordinates Network circulars, giving an overview of the participating facilities, the GW sky localization coverage, the timeline, and depth of the observations. As this event turned out to be a binary black hole merger, there is little expectation of a detectable electromagnetic (EM) signature. Nevertheless, this first broadband campaign to search for a counterpart of an Advanced LIGO source represents a milestone and highlights the broad capabilities of the transient astronomy community and the observing strategies that have been developed to pursue neutron star binary merger events. Detailed investigations of the EM data and results of the EM follow-up campaign are being disseminated in papers by the individual teams. </p

Localization and broadband follow-up of the gravitational-wave transient GW150914

A gravitational-wave transient was identified in data recorded by the Advanced LIGO detectors on 2015 September 14. The event candidate, initially designated G184098 and later given the name GW150914, is described in detail elsewhere. By prior arrangement, preliminary estimates of the time, significance, and sky location of the event were shared with 63 teams of observers covering radio, optical, near-infrared, X-ray, and gamma-ray wavelengths with ground- and space-based facilities. In this Letter we describe the low-latency analysis of the gravitational wave data and present the sky localization of the first observed compact binary merger. We summarize the follow-up observations reported by 25 teams via private Gamma-ray Coordinates Network Circulars, giving an overview of the participating facilities, the gravitational wave sky localization coverage, the timeline and depth of the observations. As this event turned out to be a binary black hole merger, there is little expectation of a detectable electromagnetic signature. Nevertheless, this first broadband campaign to search for a counterpart of an Advanced LIGO source represents a milestone and highlights the broad capabilities of the transient astronomy community and the observing strategies that have been developed to pursue neutron star binary merger events. Detailed investigations of the electromagnetic data and results of the electromagnetic follow-up campaign will be disseminated in the papers of the individual teams

Receptores de la serotonina que inhiben el tono simpático vasopresor en la rata descerebrada y desmedulada

La serotonina (5-hidroxitriptamina; 5-HT), produce simpatoinhibición vascular mediante la activación de receptores 5-HT1 presinápticos. Después de considerar los mecanismos de modulación de la unión neuroefectora, la presente revisión analiza los hallazgos que identifican el perfil farmacológico de los receptores serotoninergicos que inhiben las respuestas vasopresoras simpáticas en la rata descerebrada y desmedulada. En este sentido, se ha demostrado que la simpatoinhibición inducida por la 5-HT (i) no se modifica después de administrar solución salina o los antagonistas selectivos ritanserina (5-HT2), MDL-72222 (5-HT3) o tropisetrón (5-HT3/4); (ii) es antagonizada por la metisergida, un antagonista no selectivo de los receptores 5-HT1 y 5-HT2, en tanto que (iii) la 5-carboxamidotriptamina (5-CT), un agonista no selectivo del receptor 5-HT1, produce un efecto mimético potente, así como los agonistas selectivos 8-OH-DPAT (5-HT1A), indorrenato (5-HT1A), CP-93,129 (5-HT1B) y sumatriptán (5-HT1B/1D). Estos hallazgos demuestran la participación de los receptores simpatoinhibitorios 5-HT1. Con el uso de antagonistas selectivos, en estudios subsecuentes se demostró que la simpatoinhibición producida por el indorrenato, CP-93,129 y sumatriptán fue antagonizada en forma selectiva por, respectivamente, el WAY-100635 (5-HT1A), cianopindolol (5-HT1A/1B) y GR-127935 (5-HT1B/1D). Estos resultados indican que, en la vasculatura sistémica de la rata, los receptores simpatoinhibitorios 5-HT1 correlacionan con los subtipos 5-HT1A, 5-HT1B y 5-HT1D

Chemical properties and bactericidal activity of Rosmarinus officinalis and Origanum x majoricum

"The aim of this study was to identify the chemical properties and bactericidal activity of Rosmarinus officinalis and Origanum x majoricum in relation to the compounds detected by gas chromatographic analysis. Proceeded to wash samples Rosmarinus officinalis and Origanum x majoricum and were referred to a mashing process for seven days at room temperature with ethanol, filtering the ethanol extracts. The extracts obtained were analyzed by a gas chromatography system equipped with a mass spectrometer. Staphylococcus aureus (ATCC 25923) was used to evaluate the activity antiomicrobial extracts of Rosmarinus officinalis and Origanum x majoricum by the Kirby-Bauer method modified and quantified with the software Image J. Rosmarinus officinalis were detected alcohol, terpene and cetone compounds noted for their abundance and absence of compounds thymol and carvacol. Origanum x majoricum were identified for a considerable percentage of alcohol, acids and esters compounds, highlighting the carvacol as one of the most abundant, and linolenic acid and paeonol was detected. Antimicrobial activity of Rosmarinus officinalis extracts showed greater antimicrobial activity against Staphylococcus aureus, with respect to extract Origanum x majoricum"