Advanced Technologies for Oral Controlled Release: Cyclodextrins for oral controlled release

Cyclodextrins (CDs) are used in oral pharmaceutical formulations, by means of inclusion complexes formation, with the following advantages for the drugs: (1) solubility, dissolution rate, stability and bioavailability enhancement; (2) to modify the drug release site and/or time profile; and (3) to reduce or prevent gastrointestinal side effects and unpleasant smell or taste, to prevent drug-drug or drug-additive interactions, or even to convert oil and liquid drugs into microcrystalline or amorphous powders. A more recent trend focuses on the use of CDs as nanocarriers, a strategy that aims to design versatile delivery systems that can encapsulate drugs with better physicochemical properties for oral delivery. Thus, the aim of this work was to review the applications of the CDs and their hydrophilic derivatives on the solubility enhancement of poorly water soluble drugs in order to increase their dissolution rate and get immediate release, as well as their ability to control (to prolong or to delay) the release of drugs from solid dosage forms, either as complexes with the hydrophilic (e.g. as osmotic pumps) and/ or hydrophobic CDs. New controlled delivery systems based on nanotechonology carriers (nanoparticles and conjugates) have also been reviewed

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Optimal siting, sizing, and enforcement of marine protected areas

The design of protected areas, whether marine or terrestrial, rarely considers how people respond to the imposition of no-take sites with complete or incomplete enforcement. Consequently, these protected areas may fail to achieve their intended goal. We present and solve a spatial bio-economic model in which a manager chooses the optimal location, size, and enforcement level of a marine protected area (MPA). This manager acts as a Stackelberg leader, and her choices consider villagers’ best response to the MPA in a spatial Nash equilibrium of fishing site and effort decisions. Relevant to lower income country settings but general to other settings, we incorporate limited enforcement budgets, distance costs of traveling to fishing sites, and labor allocation to onshore wage opportunities. The optimal MPA varies markedly across alternative manager goals and budget sizes, but always induce changes in villagers’ decisions as a function of distance, dispersal, and wage. We consider MPA managers with ecological conservation goals and with economic goals, and identify the shortcomings of several common manager decision rules, including those focused on: (1) fishery outcomes rather than broader economic goals, (2) fish stocks at MPA sites rather than across the full marinescape, (3) absolute levels rather than additional values, and (4) costless enforcement. Our results demonstrate that such naïve or overly narrow decision rules can lead to inefficient MPA designs that miss economic and conservation opportunities

A Cobertura Florestal em Paisagens do Médio Vale do Rio Paraíba do Sul

RESUMO A contínua substituição da cobertura florestal pelo cultivo agrícola e a urbanização causaram alterações na maior parte do bioma Mata Atlântica no Brasil. O entendimento da interação entre os fatores físicos, antrópicos e da cobertura vegetal em uma paisagem é de fundamental importância para oferecer subsídios ao planejamento territorial de forma sustentável. Este estudo investigou a influência da altitude, declividade e orientação das vertentes na cobertura florestal em três diferentes paisagens no município de Vassouras, RJ. No geral, as áreas analisadas apresentaram a cobertura florestal fragmentada, porém foi observada uma paisagem com maior cobertura florestal do que pastagens. Entre as variáveis analisadas, a altitude e a declividade apresentaram uma relação positiva com a cobertura florestal. As paisagens estavam inseridas em diferentes contextos socioeconômicos que podem também determinar a distribuição da cobertura florestal atual. A região estudada oferece atributos socioambientais específicos de cada paisagem, cuja compreensão deve ser útil ao planejamento ambiental

Metabolic Programming during Lactation Stimulates Renal Na+ Transport in the Adult Offspring Due to an Early Impact on Local Angiotensin II Pathways

BACKGROUND: Several studies have correlated perinatal malnutrition with diseases in adulthood, giving support to the programming hypothesis. In this study, the effects of maternal undernutrition during lactation on renal Na(+)-transporters and on the local angiotensin II (Ang II) signaling cascade in rats were investigated. METHODOLOGY/PRINCIPAL FINDINGS: Female rats received a hypoproteic diet (8% protein) throughout lactation. Control and programmed offspring consumed a diet containing 20% protein after weaning. Programming caused a decrease in the number of nephrons (35%), in the area of the Bowman's capsule (30%) and the capillary tuft (30%), and increased collagen deposition in the cortex and medulla (by 175% and 700%, respectively). In programmed rats the expression of (Na(+)+K(+))ATPase in proximal tubules increased by 40%, but its activity was doubled owing to a threefold increase in affinity for K(+). Programming doubled the ouabain-insensitive Na(+)-ATPase activity with loss of its physiological response to Ang II, increased the expression of AT(1) and decreased the expression of AT(2) receptors), and caused a pronounced inhibition (90%) of protein kinase C activity with decrease in the expression of the α (24%) and ε (13%) isoforms. Activity and expression of cyclic AMP-dependent protein kinase decreased in the same proportion as the AT(2) receptors (30%). In vivo studies at 60 days revealed an increased glomerular filtration rate (GFR) (70%), increased Na(+) excretion (80%) and intense proteinuria (increase of 400% in protein excretion). Programmed rats, which had normal arterial pressure at 60 days, became hypertensive by 150 days. CONCLUSIONS/SIGNIFICANCE: Maternal protein restriction during lactation results in alterations in GFR, renal Na(+) handling and in components of the Ang II-linked regulatory pathway of renal Na(+) reabsorption. At the molecular level, they provide a framework for understanding how metabolic programming of renal mechanisms contributes to the onset of hypertension in adulthood