In Silico Evaluation of Ibuprofen and Two Benzoylpropionic Acid Derivatives with Potential Anti-Inflammatory Activity

Inflammation is a complex reaction involving cellular and molecular components and an unspecific response to a specific aggression. The use of scientific and technological innovations as a research tool combining multidisciplinary knowledge in informatics, biotechnology, chemistry and biology are essential for optimizing time and reducing costs in the drug design. Thus, the integration of these in silico techniques makes it possible to search for new anti-inflammatory drugs with better pharmacokinetic and toxicological profiles compared to commercially used drugs. This in silico study evaluated the anti-inflammatory potential of two benzoylpropionic acid derivatives (MBPA and DHBPA) using molecular docking and their thermodynamic profiles by molecular dynamics, in addition to predicting oral bioavailability, bioactivity and toxicity. In accordance to our predictions the derivatives proposed here had the potential capacity for COX-2 inhibition in the human and mice enzyme, due to containing similar interactions with the control compound (ibuprofen). Ibuprofen showed toxic predictions of hepatotoxicity (in human, mouse and rat; toxicophoric group 2-arylacetic or 3-arylpropionic acid) and irritation of the gastrointestinal tract (in human, mouse and rat; toxicophoric group alpha-substituted propionic acid or ester) confirming the literature data, as well as the efficiency of the DEREK 10.0.2 program. Moreover, the proposed compounds are predicted to have a good oral bioavailability profile and low toxicity (LD50 < 700 mg/kg) and safety when compared to the commercial compound. Therefore, future studies are necessary to confirm the anti-inflammatory potential of these compounds

Insulin resistance and carotid intima-media thickness mediate the association between resting-state heart rate variability and executive function: A path modelling study

Background: Research has linked high-frequency heart rate variability (HF-HRV) to cognitive function. The present study adopts a modern path modelling approach to understand potential causal pathways that may underpin this relationship. Methods: Here we examine the association between resting-state HF-HRV and executive function in a large sample of civil servants from Brazil (N = 8114) recruited for the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). HF-HRV was calculated from 10-min resting-state electrocardiograms. Executive function was assessed using the trail-making test (version B). Results and conclusions: Insulin resistance (a marker of type 2 diabetes mellitus) and carotid intima-media thickness (subclinical atherosclerosis) mediated the relationship between HRV and executive function in seriatim. A limitation of the present study is its cross-sectional design; therefore, conclusions must be confirmed in longitudinal study. Nevertheless, findings support that possibility that HRV provides a 'spark' that initiates a cascade of adverse downstream effects that subsequently leads to cognitive impairment.Fil: Kemp, Andrew H.. University of Sydney; Australia. Universidade de Sao Paulo; BrasilFil: Rodríguez López, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones y Estudios sobre Cultura y Sociedad. Universidad Nacional de Córdoba. Centro de Investigaciones y Estudios sobre Cultura y Sociedad; Argentina. University of Sydney; Australia. Universidad Autónoma de Madrid; EspañaFil: Passos, Valeria M. A.. Universidade Federal de Minas Gerais; BrasilFil: Bittencourt, Marcio S.. Universidade de Sao Paulo; BrasilFil: Dantas, Eduardo M.. University of Vale do São Francisco; BrasilFil: Mill, José G.. Universidade Federal do Espírito Santo; BrasilFil: Ribeiro, Antonio L. P.. Universidade Federal de Minas Gerais; BrasilFil: Thayer, Julian F.. Ohio State University; Estados UnidosFil: Bensenor, Isabela M.. Universidade de Sao Paulo; BrasilFil: Lotufo, Paulo A.. Universidade de Sao Paulo; Brasi

Braincase of panphagia protos (dinosauria, sauropodomorpha)

We describe a partial braincase of the basal sauropodomorph Panphagia protos from the Upper Triassic (midCarnian) horizons of the Ischigualasto Formation. The disarticulated braincase from a subadult individual includes one frontal, both parietals, one prootic, and the supraoccipital. The frontal is longer anteroposteriorly than it is wide transversely, has a small anterolateral process, and an elongate oval depression for the olfactory bulb. The supraoccipital is broader transversely than it is deep dorsoventrally and lacks a pronounced median nuchal eminence. Some braincase features that characterize more derived basal sauropodomorphs are not present in Panphagia, including a broader frontal and reduced anterior tympanic and floccular recesses. Panphagia appears to represent an early stage in the evolution of sauropodomorph dinosaurs.Describimos la caja craneana parcial del sauropodomorfo basal Panphagia protos proveniente de horizontes del Triásico superior (Carniano medio) de la Formación Ischigualasto. La caja craneana desarticulada es de un individuo sub-adulto e incluye un frontal, dos parietales, un proótico y el supraoccipital. El frontal es más largo anteroposteriormente que ancho transversalmente, tiene un pequeño proceso anterolateral y una depresión alargada oval para el bulbo olfatorio. El supraoccipital es transversalmente más ancho que dorsoventralmente alto y carece de una eminencia nucal media pronunciada. Algunas de las características que caracterizan los neurocráneos de sauropodomorfos basales más derivados no están presentes en Panphagia, incluyendo el frontal ancho y la reducción de las cavidades timpánica anterior y flocular. Panphagia parece representar una etapa temprana en la evolución de los dinosaurios sauropodomorfos.Fil: Martínez, Ricardo Néstor. Universidad Nacional de San Juan. Facultad de Ciencias Exactas, Fisicas y Naturales. Instituto y Museo de Ciencias Naturales; ArgentinaFil: Haro, Jose Augusto. Universidad Nacional de San Juan. Facultad de Ciencias Exactas, Fisicas y Naturales. Instituto y Museo de Ciencias Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Apaldetti, Graciela Cecilia. Universidad Nacional de San Juan. Facultad de Ciencias Exactas, Fisicas y Naturales. Instituto y Museo de Ciencias Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

PLANTAS HOSPEDEIRAS DE Thyrinteina arnobia (LEPIDOPTERA: GEOMETRIDAE) AFETAM O DESENVOLVIMENTO DO PARASITOIDE Palmistichus elaeisis (HYMENOPTERA: EULOPHIDAE)1

O objetivo deste trabalho foi avaliar a eficiência do parasitismo e a biologia da prole do parasitoide Palmistichus elaeisis Delvare e La Salle (Hymenoptera: Eulophidae) em pupas de Thyrinteina arnobia Stoll (Lepidoptera: Geometridae) quando criadas em plantas de Psidium guajava ou Eucalyptus cloeziana. Ovos de T. arnobia foram coletados e colocados em sacos de tecido tipo organza envolvendo galhos de plantas de P. guajava (T1) e E. cloeziana (T2) até as lagartas alcançarem a fase de pupa. Trinta pupas de cada tratamento foram individualizadas em tubos de vidro e expostas ao parasitismo por quatro fêmeas de P. elaeisis por 24 h. Avaliaram-se a emergência da progênie do parasitoide por pupa; a porcentagem de parasitismo, pupas mortas e de adultos de T. arnobia emergidos; a duração do ciclo de vida (ovo-adulto);a longevidade; a razão sexual; e o tamanho da cápsula cefálica e do corpo do parasitoide. A porcentagem de parasitismo, a emergência de P. elaeisis por pupa, a longevidade das fêmeas e o tamanho da cápsula cefálica e do corpo dos machos do parasitoide foram menores quando seu hospedeiro foi criado em plantas de eucalipto. Isso pode ter ocorrido devido à grande quantidade de compostos do metabolismo secundário presentes nesta planta, que podem ser acumulados no corpo do herbívoro ao se alimentar, afetando negativamente o inimigo natural. Palmistichus elaeisis mostrou-se mais adaptado à mirtácea nativa da América P. guajava

Development and reproductive performance of Hereford heifers of different frame sizes up to mating at 14-15 months of age

ABSTRACT Body development and reproductive performance of a hundred forty-two 14 to 15-month-old heifers, classified at weaning according to frame size as small, medium, and large, were evaluated. The parameters evaluated were: body weight, hip height, body condition score, weight gain, ovarian activity, and pregnancy rate. At weaning, body weight and hip height were significantly different among frame scores, (small – 133.0 kg, 92.2 cm; medium – 158.5 kg, 96.6 cm; and large – 185.2 kg; 100.2 cm). After weaning, heifers grazed together on natural pastures during the autumn and on ryegrass (Lolium multiflorum La.) during the winter and spring. Frame score differences remained until the beginning of the breeding season (BS), starting on average at 14 months of age. Weight gain between weaning and the beginning of BS was not different among frame scores (0.740 kg/day, on average). Body weights at the beginning of the BS were significantly different, of 255.7 kg (53.3% of the mature weight) for small heifers, 285.0 kg (59.4%) for medium heifers, and 307.6 kg (64.1%) for large heifers. Ovarian activity at the beginning of the BS was not different among the three groups. The average weight gain values during the BS of 0.492, 0.472, and 0.421 kg/day for small, medium, and large heifers, respectively, were significantly different. Pregnancy rates were not different among groups (small, 71.4%; medium, 76.4%; and large, 76.5%). Frame score did not influence the reproductive performance of heifers, but the small and medium heifers conceived 29 and 20 days earlier, respectively, than the large heifers