Beneficial effects of the ethanol extract of Caesalpinia pyramidalis on the inflammatory response and abdominal hyperalgesia in rats with acute pancreatitis

AbstractEthnopharmacological relevanceCaesalpinia pyramidalis Tul. (Fabaceae) is a plant found in the Northeast of Brazil that is popularly used to treat inflammation. Acute pancreatitis (AP) is an inflammatory disease for which abdominal pain is a relevant symptom. As there is no specific therapy for AP, we investigated the effect of the ethanol extract from the inner bark of C. pyramidalis (EECp) on the AP induced by common bile duct obstruction (CBDO) in rats.Material and methodsAP was induced in male Wistar rats (200–250g, n=6–8) through laparotomy and subsequent CBDO. Animals were euthanized after 6 (G6h) or 24h (G24h) of induction. In the G6h protocol, animals were pretreated with EECp (100–400mg/kg, p.o.) or vehicle (Tween 80; 0.2%) 1h before CBDO or sham surgery. For the G24h protocol, rats were pretreated with EECp (400mg/kg, 1h before CBDO or 1h before and 12h after CBDO) or vehicle. The following parameters were measured: inflammatory/oxidative (myeloperoxidase activity and malondialdehyde formation in the pancreas and lung, leukocyte counts in the blood and serum nitrate/nitrite), enzymatic (serum amylase and lipase levels) and nociceptive (abdominal hyperalgesia).ResultsInduction of AP by CBDO significantly increased all the parameters evaluated in both G6h and G24h protocols when compared with the respective sham group. In the G6h protocol, the EECp pretreatment (400mg/kg) significantly reduced all these parameters, besides completely inhibiting abdominal hyperalgesia. The same profile of reduction was observed from two administrations of EECp in the G24h protocol, while one single dose of EECp was able to significantly reduce pancreatic MDA, serum lipase levels, leukocyte counts in the blood and abdominal hyperalgesia without affecting the other parameters in the G24h protocol. Furthermore, rutin was found in the EECp.ConclusionsOur results demonstrated that EECp decreases inflammation, lipoperoxidation and hyperalgesia in CBDO-induced AP, making it of interest in future approaches to treat this condition

The Science of Sungrazers, Sunskirters, and Other Near-Sun Comets

This review addresses our current understanding of comets that venture close to the Sun, and are hence exposed to much more extreme conditions than comets that are typically studied from Earth. The extreme solar heating and plasma environments that these objects encounter change many aspects of their behaviour, thus yielding valuable information on both the comets themselves that complements other data we have on primitive solar system bodies, as well as on the near-solar environment which they traverse. We propose clear definitions for these comets: We use the term near-Sun comets to encompass all objects that pass sunward of the perihelion distance of planet Mercury (0.307 AU). Sunskirters are defined as objects that pass within 33 solar radii of the Sun’s centre, equal to half of Mercury’s perihelion distance, and the commonly-used phrase sungrazers to be objects that reach perihelion within 3.45 solar radii, i.e. the fluid Roche limit. Finally, comets with orbits that intersect the solar photosphere are termed sundivers. We summarize past studies of these objects, as well as the instruments and facilities used to study them, including space-based platforms that have led to a recent revolution in the quantity and quality of relevant observations. Relevant comet populations are described, including the Kreutz, Marsden, Kracht, and Meyer groups, near-Sun asteroids, and a brief discussion of their origins. The importance of light curves and the clues they provide on cometary composition are emphasized, together with what information has been gleaned about nucleus parameters, including the sizes and masses of objects and their families, and their tensile strengths. The physical processes occurring at these objects are considered in some detail, including the disruption of nuclei, sublimation, and ionisation, and we consider the mass, momentum, and energy loss of comets in the corona and those that venture to lower altitudes. The different components of comae and tails are described, including dust, neutral and ionised gases, their chemical reactions, and their contributions to the near-Sun environment. Comet-solar wind interactions are discussed, including the use of comets as probes of solar wind and coronal conditions in their vicinities. We address the relevance of work on comets near the Sun to similar objects orbiting other stars, and conclude with a discussion of future directions for the field and the planned ground- and space-based facilities that will allow us to address those science topics

TNOs are cool: a survey of the transneptunian region

Over one thousand objects have so far been discovered orbiting beyond Neptune. These trans-Neptunian objects (TNOs) represent the primitive remnants of the planetesimal disk from which the planets formed and are perhaps analogous to the unseen dust parent-bodies in debris disks observed around other main-sequence stars. The dynamical and physical properties of these bodies provide unique and important constraints on formation and evolution models of the Solar System. While the dynamical architecture in this region (also known as the Kuiper Belt) is becoming relatively clear, the physical properties of the objects are still largely unexplored. In particular, fundamental parameters such as size, albedo, density and thermal properties are difficult to measure. Measurements of thermal emission, which peaks at far-IR wavelengths, offer the best means available to determine the physical properties. While Spitzer has provided some results, notably revealing a large albedo diversity in this population, the increased sensitivity of Herschel and its superior wavelength coverage should permit profound advances in the field. Within our accepted project we propose to perform radiometric measurements of 139 objects, including 25 known multiple systems. When combined with measurements of the dust population beyond Neptune (e.g. from the New Horizons mission to Pluto), our results will provide a benchmark for understanding the Solar debris disk, and extra-solar ones as well

Enraizamento de estacas, crescimento e respostas anatômicas de mudas clonais de cacaueiro ao ácido indol-3-butírico Stem cutting rooting, growth and anatomical responses of cacao tree clonal changes to the indole-3-butyric acid

Avaliaram-se os efeitos do ácido indol-3-butírico (AIB) no crescimento e na morfologia interna de quatro clones de Theobroma cacao (CCN-10, CP-53, PS-1319 e CA-1.4). O AIB foi aplicado na base da estaca de caule, em talco inerte, nas concentrações de 2; 4; 6 e 8 g kg-1, juntamente com o controle (sem AIB). A avaliação do crescimento de raízes, caule e folhas dos quatro clones foi realizada aos 160 dias após o estaqueamento (DAE) para todas as concentrações de AIB, período também em que se realizou a coleta de material para os estudos anatômicos dos diversos órgãos, mas somente para a concentração de 4g kg-1 AIB e o controle. O clone CA-1.4 apresentou incremento na biomassa seca de raiz (BSR) com o aumento das concentrações de AIB, ao passo que, nos demais clones, houve diminuições de BSR a partir dos 4 g kg-1 AIB. O mesmo fato foi observado para a biomassa seca de caule (BSC) e de folha (BSF), exceto para a BSC do CCN-10 que não respondeu ao incremento das concentrações de AIB. Houve aumento de área foliar total para os clones CP-53 e PS-1319 com o incremento de AIB até 4 g kg-1, enquanto o aumento do número de folhas ocorreu somente para os clones CA-1.4 e CP-53 até as concentrações 8 e 4 g kg-1 AIB, respectivamente. Houve diminuição do número de estacas mortas para os clones CA-1.4 e CCN-10 até 8 g kg-1 de AIB e para o CP-53 até 4 g kg-1 de AIB. As melhores concentrações de AIB para o enraizamento de estacas de ramos dos clones de cacaueiros CP-53, PS-1319 e CCN-10 foram de 4, 4 e 6 g kg-1 AIB, respectivamente, enquanto para o clone CA-1.4 foi de 8 g kg-1 AIB; o aumento da concentração de AIB promoveu mudanças anatômicas nos órgãos vegetativos de todos os clones, influenciando na atividade do câmbio vascular e induzindo a formação de um maior número de raízes adventícias nas estacas.<br>The effects of indole-3-butyric acid (IBA) on growth and internal morphology of four clones of Theobroma cacao (CCN-10, CP-53, PS-1319 and CA-1.4) were evaluated. The IBA was applied in the base of stem cuttings, as an inert talc, in mixture concentrations of 2, 4, 6 and 8 g kg-1 together with the control, without IBA. The evaluation of the growth of roots, stem and leaves of the four clones were accomplished by 160 days after the cutting (DAC) for all the IBA concentrations. However, the anatomical studies of the several plant organs were also made to the 160 DAC, but only for the concentration of 4g kg-1 IBA and the control. The clone CA-1.4 presented increment in the root dry biomass (RDB) with the increase of the IBA concentrations, while for the other clones there were decreases of RDB starting from the 4 g kg-1 IBA. The same fact was observed for the stem and leaf dry biomass, except for CCN-10 that did not answer to the increment of the concentrations of IBA. There was an increase of the total leaf area for the clones CP-53 e PS-1319 with the increment of the IBA (concentration up to 4 g kg-1), while the leaves number only increased for the clones CA-1.4 and CP-53, concentrations up to 8 and 4 g kg-1 IBA, respectively. There was a decrease in the number of dead cuttings for the clones CA-1.4 and CCN-10 (up 8 g kg-1) of IBA and for the CP-53 (up to 4 g kg-1 of IBA). The best IBA concentrations for the branch cutting rooting of the cacao clones CP-53, PS-1319 and CCN-10 were of 4, 4 and 6 g kg-1 respectively, while for the clone CA-1.4 was the one of 8 g kg-1; the increase of the IBA concentration promoted anatomical changes in the plant organs of all the clones, influencing the activity of the vascular cambium in the stem and inducing the formation of a larger number of adventitious roots in the stem cuttings

Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation

GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the 'iCOGS' genotyping array and impute genotypes for a further 1,284 using 1000 Genomes Project data. All but two, strongly correlated SNPs (rs4442975 G/T and rs6721996 G/A) are excluded as candidate causal variants at odds against >100:1. The best functional candidate, rs4442975, is associated with oestrogen receptor positive (ER+) disease with an odds ratio (OR) in Europeans of 0.85 (95% confidence interval=0.84-0.87; P=1.7 × 10-43) per t-allele. This SNP flanks a transcriptional enhancer that physically interacts with the promoter of IGFBP5 (encoding insulin-like growth factor-binding protein 5) and displays allele-specific gene expression, FOXA1 binding and chromatin looping. Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of IGFBP5, a gene with known roles in breast cell biology

Antiinflammatory therapy with canakinumab for atherosclerotic disease

BACKGROUND: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. METHODS: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P=0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P=0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P=0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P=0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P=0.31). CONCLUSIONS: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. Copyright © 2017 Massachusetts Medical Society