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Elaborar una propuesta multidisciplinar de criterios de cribado de enfermedad pulmonar intersticial difusa (EPID) en pacientes con artritis reumatoide (AR) y, a la inversa, que sirvan de referencia en la derivación entre los servicios de Reumatología y Neumología para la detección precoz de estos pacientes. Se revisó de forma sistemática la literatura sobre factores de riesgo para el desarrollo de EPID en la AR, la utilidad de los distintos métodos diagnósticos para su identificación en pacientes con AR y las diferentes propuestas de criterios de derivación a Reumatología por sospecha de AR precoz. Basándose en la evidencia disponible y en su experiencia clínica, un comité científico formado por dos reumatólogos y dos neumólogos propuso unos criterios de cribado que fueron evaluados mediante el método Delphi por un panel de siete neumólogos y siete reumatólogos. Todos los participantes eran expertos en esta patología. Se han elaborado unos criterios para el cribado de EPID en pacientes diagnosticados de AR, y unos criterios para la detección precoz de AR en casos de EPID de causa no filiada. Se incluyen también propuestas sobre las pruebas complementarias a realizar en los diferentes escenarios clínicos considerados y sobre la periodicidad con la que debe repetirse el cribado. Se propone por primera vez una estrategia de cribado selectivo para el diagnóstico precoz de los pacientes con EPID-AR. Esta propuesta pretende resolver algunos interrogantes clínicos habituales y facilitar la toma de decisiones. Los criterios propuestos deben ser evaluados en futuros estudios de validación. To develop a joint proposal for screening criteria of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) and vice versa, which serves as a guidelines in patient referral between the Rheumatology and Pneumology departments to early detection of these patients. A systematic literature review was carried out on the risk factors for the development of ILD in RA patients, and for the referral criteria to Rheumatology for suspected early RA. Based on the available evidence, screening criteria were agreed using the Delphi method by a panel of pneumologists and rheumatologists with expertise in these pathologies. Screening criteria for ILD in patients with RA and for the early detection of RA in cases with ILD of unknown etiology have been developed. In both cases, a detection strategy was based on clinical risk factors. Recommendations also included the complementary tests to be carried out in the different clinical scenarios and on the periodicity that screening should be repeated. A selective screening strategy is recommended for the first time in the early diagnosis of patients with ILD-RA. This multidisciplinary proposal aims to solve some common clinical questions and help decision-making, although its usefulness to identify these patients with good sensitivity must be confirmed in a validation study. [ABSTRACT FROM AUTHOR]

Inflammatory diseases, as periodontal disease (PD), has been associated with disturbance of lipid and glycemic metabolisms, as demonstrated by the increasing of PD patients with type 2 diabetes mellitus (T2D) and/or dyslipidemia comorbidities. We aimed to investigate the expression of inflammation and lipid metabolism genes, and correlations among clinical and biochemical characteristics in normoglycemic or T2D patients with dyslipidemia and PD, in comparison with healthy individuals. Five groups of 30 individuals each (150 patients) were formed based upon T2D, dyslipidemic and periodontal status. Blood analyses of lipid and glycemic profiles were carried out, and the gene expression was assessed by RT-qPCR. The systemic expression of IL6, TNFA and LEP genes were significantly higher in T2D, dyslipidemia and PD patients, while the PECAM1 gene showed the opposite. Higher RETN levels were found in patients with T2D independently of their glycemic control status. There were positive correlations between: TNFA, LEP and RETN with worse periodontal parameters; IL6 , TNFA , ADIPOR1 , LEP and RETN with waist-to-hip ratio ; glycemic parameters with RETN; total cholesterol and triglycerides with LEP expression. We conclude that pro-inflammatory cytokines were related with worse lipid, glycemic and periodontal parameters, reinforcing that a hyper-inflammatory status connects systemic and oral inflammatory diseases. • IL6 and TNFA were higher expressed in patients with chronic periodontitis. • LEP was higher expressed in patients with dyslipidemia, while PECAM1 showed lower expression in the same patients. • Higher RETN levels were found in patients with type 2 diabetes independently of their glycemic control status. • The glycemic control, lipid profile, and periodontal status could proportionally influence alterations in the systemic expression of pro-inflammatory genes such as IL6 and TNFA, as well as important genes to lipid metabolism such as LEP, ADIPOQ, ADIPOR1 and RETN. • These findings reinforce the evidence that a hyper-inflammatory status connect systemic and oral inflammatory diseases, such as type 2 diabetes, dyslipidemia and chronic periodontitis. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Byrsonima intermedia is a species of bush popularly used to treat gastrointestinal disorders, such as gastric ulcers, gastritis, and diarrhea. Previous studies have revealed that the methanolic crude extract of B. intermedia leaves has gastroprotective and healing properties. In this new study, we specifically investigated two purified partitions, ethyl acetate (EtOAc) and water (AcoAq), obtained from the crude extract to characterize the antiulcer effects of these two partitions and the mechanisms of action of this medicinal plant. The healing effects of these partitions on the gastric and duodenal mucosa were assessed after ischemia-reperfusion (I/R) or acetic acid-induced injury. The involvement of tumor necrosis factor-alpha (TNF-alpha), interleukin 1β (IL-1β), interleukin 10 (IL-10), and myeloperoxidase (MPO) activity and glutathione (GSH) levels were determined. The antibacterial activity against Helicobacter pylori was evaluated using microdilution methods. The phytochemical analysis of AcoAq revealed a predominance of oligomeric proanthocyanidins and galloyl quinic esters, whereas EtOAc was found to contain concentrated flavonoids. Both partitions led to a significant reduction in gastric lesions, but AcoAq was more effective than EtOAc with regard to anti- Helicobacter pylori activity in addition to protecting the gastric mucosa against ethanol, non-steroidal anti-inflammatory drugs (NSAIDs) and duodenal mucosal damage induced by cysteamine. Additionally, both partitions were associated with a significant increase in gastric and duodenal healing and increased gastric mucosal GSH content after damage induced by acetic acid. On the other hand, after 6 days of treatment, EtOAc was more effective than AcoAq in ameliorating gastric damage upon initiation of the gastric I/R, which was accompanied by a significant reduction in the activity of gastric mucosal MPO, IL 1-β and TNF-alpha, as well as an elevation in IL-10 and GSH content. These results demonstrate that the oligomeric proanthocyanidins and galloyl quinic esters present in AcoAq were more effective in the prevention of gastric and duodenal ulcers due to the antioxidant effects of these compounds, whereas the flavonoids present in EtOAc were more effective due to their anti-inflammatory activity on the gastric and duodenal tissue. All these results confirm that the rich phytochemical diversity of B. intermedia contributes to the pharmacological actions of this medicinal plant on the gastrointestinal tract in addition to its activity against H. pylori. [ABSTRACT FROM AUTHOR]

Neurofibroma is the main benign neoplasm of the neural sheath. A 35-year-old, brown, female patient, uopn intraoral examination, presented a bilobulated nodular lesion with a sessile base, non-bleeding, an absence of central papillae, painless, firm on palpation, reddish in color, circumscribed, well-defined, measuring approximately 15mm, and located on the lingual dorsum near the left lateral border. According to a clinical diagnosis of schawannoma, the lesion was submitted to excisional biopsy. Microscopically, a partially encapsulated, circumscribed tissue of neural origin was observed, comprised mainly of thin, wavy spindle cells arranged in an irregular pattern and the presence of collagen fibers. The surface epithelium showed atrophy of the epithelial ridges and areas of acanthosis. The underlying connective tissue exhibited vascular neoformations. Through histochemical staining by Wade's method, mast cells were observed. The histopathological diagnosis indicated neurofibroma. The patient is undergoing follow-up with no recurrence after 30 months. [ABSTRACT FROM AUTHOR]

The current chromatographic approaches used in protein purification are not keeping pace with the increasing biopharmaceutical market demand. With the upstream improvements, the bottleneck shifted towards the downstream process. New approaches rely in Anything But Chromatography methodologies and revisiting former techniques with a bioprocess perspective. Protein crystallization and precipitation methods are already implemented in the downstream process of diverse therapeutic biological macromolecules, overcoming the current chromatographic bottlenecks. Promising work is being developed in order to implement crystallization and precipitation in the purification pipeline of high value therapeutic molecules. This review focuses in the role of these two methodologies in current industrial purification processes, and highlights their potential implementation in the purification pipeline of high value therapeutic molecules, overcoming chromatographic holdups. [ABSTRACT FROM AUTHOR]

Chlorella vulgaris cultivation in two-stage process was applied to increase the lipid productivity without compromising the biomass productivity. At the first stage, microalgae was cultivated under nutrient sufficient conditions to obtain a maximized cell density; at the second stage, nitrate conditions are changed to trigger the accumulation of TAG. During first stage, the maximum biomass productivity (32 mg L −1 d −1 ) was observed after 13 days under nutrient sufficient conditions with 1.21 g L −1 NaNO 3 and 0.00449 g L −1 K 2 HPO 4 . Maximum lipid content (25.4% DW), lipid productivity (7.5 mg L −1 d −1 ) and TAG content (41.3% in total lipids) were favored by the nitrogen starvation conditions for more 4 days, at the second stage. Oil extracted at the second stage contained lower percentage of PUFAs being more suitable for the biodiesel production when compared with the oil extracted at the first stage. This two-stage phototrophic process is promising to provide a more efficient way for on a large-scale production of algal biomass and biodiesel production. [ABSTRACT FROM AUTHOR]

The feasibility of sugarcane vinasse as supplement in growth medium of Spirulina maxima was investigated. The cell was cultivated under autotrophic (no vinasse, 70 μmol photons m −2 s −1 ), heterotrophic (no light, culture medium supplemented with vinasse at 0.1% v/v and 1.0% v/v) and mixotrophic conditions (70 μmol photons m −2 s −1 , vinasse at 0.1% v/v and 1.0% v/v). These preliminary results suggested a cyclic two-stage cultivation – CTSC, with autotrophic condition during light phase of the photoperiod (12 h, 70–200 μmol photons m −2 s −1 ) and heterotrophic condition during dark phase (12 h, 3.0% v/v vinasse). The adopted CTSC strategy consisted in three cycles with 75% withdrawal of suspension and reposition of medium containing 3.0% v/v vinasse, separated by autotrophic rest periods of few days between cycles. Results show an increase of biomass concentration between 0.495 g L −1 and 0.609 g L −1 at the 7th day of each cycle and high protein content (between 74.3% and 77.3% w/w). [ABSTRACT FROM AUTHOR]

Intertidal foreshore sediments from a 110 km stretch of the Thames Estuary were analysed for glycerol dialkyl glycerol tetraethers (GDGTs) to track soil organic matter (OM) input and evaluate the impact of coastal urbanisation on their distribution. Concentration of branched (br)GDGTs ranged from < 1 to 15 μg/g organic carbon (OC) and crenarchaeol ranged from 0.6 to 19 μg/g OC. An overall decrease in brGDGTs was observed from the inner Thames (Brentford) to the outer Thames (Isle of Grain), suggesting a drop in soil OM input towards the sea. In contrast, crenarchaeol concentration was highest around east London rather than towards the open sea. Such elevated crenarchaeol concentration occurred in the section of the river most influenced by anthropogenic pollution, such as discharge points for London’s major sewage treatment plants, docks and power plants. The non-systematic spatial distribution of crenarchaeol was also reflected in the branched isoprenoid tetraether (BIT) index. The highest BIT values occurred upstream and in close proximity to salt marshes (0.8–1), whereas the lowest values (0.3–0.5) were towards the sea. However, unusually low values (0.4) were observed in the river section that had high crenarchaeol concentration. In contrast, bulk δ 13 C values were insensitive to London’s anthropogenic influence. This suggests that the natural systematic decrease in BIT index in the estuary is overprinted by London’s anthropogenic activity between Deptford Creek and Tilbury. We therefore advise caution when interpreting the BIT index for sediments in close proximity to megacities discharging industrial and municipal waste that can become incorporated into the near surface sedimentary record. [ABSTRACT FROM AUTHOR]

Abstract: Steryl alkyl ethers (SAEs) have been reported from marine sediments ranging from Holocene to Lower Cretaceous and their production has been linked to upwelling of cold, nutrient-rich water. However, the lack of continuous stratigraphic records for them has complicated validation of the precise connection of their production, sedimentary distribution and survival to climatic conditions. Here, we report an SAE record that spans the last ca. 135ka from a core taken offshore southeastern Australia in the Murray Canyons Group region. The SAEs are composed predominantly of C27–C30 steroid moieties with one or two double bonds, ether-bound to C10–C11 alkyl moieties. Some of the SAEs are identical to those reported in marine sediments, whereas others have not been identified previously. They do not exhibit any systematic change in distribution over the past 110ka but sediments older than 110ka possess a different assemblage, with a higher amount of constituents containing a C11 alkyl moiety. The SAE accumulation rate increases rapidly during glacial episodes and for intervals characterized by a sharp decline in sea-surface temperature. The results suggest that SAEs may be related to marine eukaryotes that thrive when there is an influx of cold, deep waters in the Murray Canyons Group region, likely triggered by stronger westerlies over southeastern Australia forcing deeper water to reach the surface during glacials. [Copyright &y& Elsevier]

Sedimentary organic pollution in the urban reaches of the Thames estuary is changing from fossil fuel hydrocarbons to emerging synthetic chemicals. De-industrialisation of London was assessed in three cores from Chiswick (Ait/Eyot) mud island using pharmaceuticals, faecal sterols, hydrocarbons (TPH, PAH), Black Carbon (BC) and organotins (TBT). These ranked in the order; BC 7590-30219 mg/kg, mean 16,000 mg/kg > TPH 770–4301, mean 1316 mg/kg > Σ16PAH 6.93–107.64, mean 36.46 mg/kg > coprostanol 0.0091–0.42 mg/kg, mean of 0.146 mg/kg > pharmaceuticals 2.4–84.8 μg/kg, mean 25 μg/kg. Hydrocarbons co-varied down-profile revealing rise (1940s), peak (1950s -1960s) and fall (1980s) and an overall 3 to 25-fold decrease. In contrast, antibiotics, anti-inflammatory (ibuprofen, paracetamol) and hormone (17β-estradiol) increased 3 to 50-fold toward surface paralleling increasing use (1970s-2018). The anti-epileptics, carbamazepine and epoxcarbamazepine showed appreciable down-core mobility. Faecal sterols confirmed non-systematic incorporation of treated sewage. Comparison to UK sediment quality guidelines indicate exceedance of AL2 for PAH whereas TBT was below AL1. [Display omitted] • Pharmaceuticals (antibiotics) are rapidly increasing in urban estuarine sediments • Fossil fuel pollution and antifouling organo‑tins have declined but still present • Polycyclic aromatic hydrocarbons are above sediment quality guidelines • Black carbon exerts a strong control over sedimentary pollution in London • Sewage deposition is variable and sourced from both treated and untreated faeces • Antiepileptics, carbamazepine and epoxycarbamazipine are mobile in sediment [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Ethnopharmacological survey indicated leaves of Byrsonima fagifolia Nied. (Malpighiaceae) against gastrointestinal disorders. Aim of the study: The methanolic extract from the leaves of Byrsonima fagifolia (denominated BF) was evaluated for toxic, mutagenic, gastroprotective, antidiarrheal, antibacterial and immunomodulatory activities. Materials and methods: The preventive and healing action of BF against gastric ulcer was evaluated in experimental models in rodents. We evaluated immunomodulatory (by murine peritoneal macrophages), antidiarrheal (by induced diarrhea with castor oil and intestinal motility) and antibacterial action of BF against standard strain of Escherichia coli, Staphylococcus aureus and Helicobacter pylori. The safety of use of BF was also evaluated by mutagenic (Ames assay) and by analyses of toxicity parameters. Results: Phytochemical BF profile indicated the presence of phenolic compounds with antioxidant and radical-scavenging properties. BF significantly inhibited gastric lesions induced by ethanol and HCl/ethanol and endogenous mucosal sulphydryl groups (SHs) participated efficaciously in BF gastroprotection. BF blocked development of inflammation process and also has antidiarrheal actions. This extract accelerated the healing of the gastric ulcerated mucosa by stimulating proliferative factors and by increasing production of gastric mucus with no toxic action. The substances responsible for the protective action are concentrated in the ethyl acetate fraction that demonstrated no mutagenic action in vitro. Conclusions: Byrsonima fagifolia presents gastroprotective, healing and antidiarrheal activities supporting previous claims that its traditional use by Brazilians can treat these gastrointestinal ailments. [Copyright &y& Elsevier]

The oil spill off the coast of the Brazilian Northeast region is one of the most significant global events regarding contamination and environmental impact in recent years. This work evaluates the effects of oil spills on the Northeast coasts between Alagoas and Sergipe states from October 2019 to January 2020. Analysis of some sampling points of seawater revealed the presence of Hg, Cd, Pb, and Cu in levels above the maximum concentration limits established by the Brazilian legislation. For water quality parameters, phosphorus, nitrite, and turbidity showed statistically different values. However, the chromatographic profiles of oil obtained from different beaches were quite similar. Seawater, fishes, and massunins (bivalve) presented the main polycyclic aromatic hydrocarbons: naphthalene, phenanthrene, fluoranthene, fluorene, and acenaphthalene. Therefore, the concentration of organic and inorganic contaminants determined in different environmental locations served as a subsidy to assess the effect of the preliminary oil spill on the Brazilian coast. [Display omitted] • Analysis of oil, water, bivalves, and fish related to the oil disaster in the Brazilian Northeast coastal undertaken. • Crude oil samples presented Hg, As, Cd, Pb, and Zn in the highest concentrations. • The total PAH concentrations in the seawater samples varied from <0.01 to 275.49 ng L-1. • Naphthalene was the major contributor to the total concentration of 16 PAH analyzed. • Total PAH concentrations per fish sample ranged from 14.28 to 32.06 ng g-1. [ABSTRACT FROM AUTHOR]

Abstract: We have developed a novel method, based on high performance liquid chromatography–mass spectrometry, for the rapid and quantitative analysis of levoglucosan in geological samples. Compared with existing methods, it does not require derivatization or extensive work up, and requires less sample material. Its validity is demonstrated by way of application to soil samples collected from a burned dune area and a late Quaternary marine sediment. [Copyright &y& Elsevier]

• n -alkane and brGDGT analysed to assess terrestrial C input in the Conwy Estuary. • Biomarkers in sediments showed a higher terrestrial influence compared to marine OC. • Molecular and bulk proxies compromised due to mixed source of compounds. • Similar concentration and fractional distribution of brGDGT in three UK estuaries. Owing to their restricted riverine flow and greater numbers, small estuaries (annual discharge < 2000 m3 s−1) are important sites of organic carbon (OC) storage in sediments. The Conwy Estuary is an exemplar small rural-agricultural catchment which delivers a diverse pool of terrestrial OC to the Irish Sea. Thirty-nine surface sediments, covering a distance of 10.5 km, were taken transversal as well as longitudinal to the estuary to examine local and distant catchment inputs. Biomarkers (branched Glycerol Dialkyl Glycerol Tetraethers - brGDGTs, n -alkanes) and molecular and bulk proxies (BIT, P aq , TAR, δ13C, C/N), showed sediments were dominated by terrestrial inputs, with only sediments of the three most seaward sites showing stronger physical and geochemical characteristics of a marine influence (e.g., sandier sediments and lower BIT). Biomarker concentrations in the Conwy were comparable to the more urbanised Thames and the Clyde estuaries. The three estuaries showed similar fractional abundance of the brGDGTs, recording an inverse trend between the hexamethylated and the tetramethylated brGDGTs, and showing the pentamethylated brGDGTs as the dominant group. A systematic decrease in terrestrial biomarkers from bank to the main channel confirmed either a strong localised erosion/runoff process or a decrease in water velocity leading to a higher deposition. [ABSTRACT FROM AUTHOR]

Abstract The exploitation of lakes has led to large-scale contemporary impacts on freshwater systems, largely in response to catchment clearance. Such clearance is causing changes to carbon dynamics in tropical lakes which may have significance for wider carbon budgets, depending on the changes in carbon sequestration and mineralisation driven by changing roles of terrestrial and aquatic carbon in lakes over time. Despite increasing awareness of the pivotal role of carbon source in carbon dynamics, discriminating the source of carbon from a palaeolimnological record is rarely undertaken. Here we use novel geochemical techniques (brGDGTs, n -alkanes, Rock-Eval pyrolysis), paired with traditional analyses (diatoms, pollen), to elucidate changing sources of carbon through time and ecosystem response. Environmental changes at Lake Nyamogusingiri can be divided into three phases: Phase I (CE 1150–1275), a shallow and productive lake, where a diverse terrestrial environment is, initially, the main carbon source, before switching to an aquatic source; Phase II (CE 1275–1900), variable lake levels (generally in decline) with increasing productivity, and carbon is autochthonous in source; Phase III (CE 1900–2007), lake level declines, and the carbon is of a mixed source, though the terrestrially derived carbon is from a less diverse source. The organic geochemical analyses provide a wealth of data regarding the complexity of aquatic response to catchment and with-in lake changes. These data demonstrate that small, tropical lake systems have the potential to bury high quantities of carbon, which has implications for the disruption of local biogeochemical cycles (C, P, N, and Si) both in the past, and the future as human and climate pressures increase. Highlights • Novel organic geochemical techniques discriminate carbon sources through time. • Offers insight into the complexity and functionality of a lake system through time. • Organic geochemistry elucidates findings derived from diatom and pollen analyses. • Small tropical lakes have potential to bury large quantities of terrestrial carbon. [ABSTRACT FROM AUTHOR]

The UN Sustainable Development Goals highlight the myriad of socio-economic and environmental challenges occurring as a result of anthropogenic chemical pollution. Urban sediments from informal settlements (slums) on the Nairobi, Ngong and Mathare Rivers (n = 25), were evaluated for sediment quality. Microtox bioassay identified 8 sites as toxic, 9 as moderately toxic and 8 as non-toxic. Slum sediments were characterised by high total organic carbon and Rock-Eval pyrolysis revealed bound carbon from a mix of raw sewage and domestic refuse. Sediments from Kiambio, Kibera, Mathare and Kawangware slums contained high coprostanol at 55–298 μg/g and epicoprostanol at 3.2–21.7 μg/g confirming appreciable incorporation of untreated human faeces. Hormones, antianalgeiscs, antiinflamatories, antiepileptics and antibiotics most affected Mathare > Kiambio > Kibera > Mukuru > Kawangware slums. Carbamazepine, ibuprofen, diclofenac and acetaminophen concentrations are amongst the highest reported in Kenyan river sediments and were positively correlated with faecal steroids (sewage). Common persistent organic pollutants, such as organochlorine insecticides ΣDDT 1–59 μg/kg, mean 21.2 μg/kg, Σ16PAH 182–2218 μg/kg, mean 822 μg/kg and Σ30 PCB 3.1–157.1 μg/kg, mean of 21.4 μg/kg were between probable effect likely and unlikely sediment quality guidelines (SQG). PAH source ratios and parent to alkyl-PAH distribution suggested vehicle exhaust, power stations (heavy oil), kerosene (cooking oil) and other pollution sources. Trace metal concentrations As, Cd, Cr, Hg and Ni were below SQG whereas Pb exceeded the SQG. This multi-contaminant characterisation of sediment quality in Nairobi supports the development and implementation of policies to improve urban infrastructure to protect ecological and human health. It demonstrates the need for environmental geochemists to engage in the science-policy interface associated with both global and national development frameworks, with particular reference to the Sustainable Development Goals, New Urban Agenda, and Kenya's Vision 2030. • Urban slum river sediments of Nairobi are polluted with a mix of raw sewage and domestic refuse that presents a risk to human and ecological health. • Emerging pharmaceutical contamination (hormones, antibiotics antiinflamatories) are widespread. • PAH, PCB, DDT pollutants are ubiquitous but are between effect likely and unlikely sediment quality guidelines. • Nairobi slum sediments are toxic and contain a cocktail of organic contaminants but are low in most trace metals. [ABSTRACT FROM AUTHOR]

Highlights: [•] β-Myrcene contributed to the maintenance of integrity of the gastric mucosa. [•] Significant decrease in the I/R-induced ulcerative lesions was ascribed by β-myrcene. [•] Increased lipid peroxidative damage in ulcer was attenuated by β-myrcene. [•] β-Myrcene and increasing GSH levels and prevented the depletion of GSH, GR and GPx. [•] The data define a potential role for β-myrcene against peptic ulcer disease. [ABSTRACT FROM AUTHOR]

Abstract: In the present work, mesoporous silica SBA-16 nanoparticles with an innovative cubic mesoporous matrix, practically unexplored in terms of functionalization and in vitro studies, has been synthesized and functionalized using two different silanizing agents: 3-amino-propyl-triethoxysilane (APTES) and n-propyltriethoxysilane (PTES). The pure and functionalized silica nanoparticles were physicochemically and morphologically characterized, the results of which presented adequate characteristics for in vitro and in vivo applications. The influence of the functionalization process on the incorporation rate and kinetic release of a model drug (Atenolol) was also studied. These results revealed that samples functionalized with APTES presented a negligible release of Atenolol from the nanoparticles in simulated body fluid (SBF). This is an important result when seeking to avoid the premature release of chemotherapeutic agents or radioisotopes into the bloodstream until it reaches its final destination. Finally, the cytocompatibility in vitro tests were conducted in an MRC-5 cell line, human fetal lung fibroblast cells, at different concentrations. The results indicated no significant change in cell morphology, chromosomal changes, or increase of ROS in the MRC-5 cells related to the control group. All findings from this study reveal a potential application of mesoporous silica SBA-16 nanoparticles as new potential drugs or radioisotope nanocarriers to be applied in therapeutic or diagnostic procedures. [Copyright &y& Elsevier]

Abstract: The present work describes the preparation, labeling, physicochemical characterization, and in vitro cytotoxic evaluation of long circulating pH-sensitive liposomes containing 159Gd-DTPA-BMA. These liposomes were successfully obtained and submitted to neutron irradiation for gadolinium labeling. Their size, distribution, and homogeneity were determined by photon correlation spectroscopy, while their zeta potential was determined by laser Doppler anemometry. The morphology and structural organization were evaluated by atomic force microscopy. The stability and release profiles of Gd-DTPA-BMA in the liposomes were determined in vitro in Dubelco''s Modified Eagle''s Medium and rat serum at 70%. The results showed that liposomes remained physically stable after 8h of irradiation and presented a low release profile of its content in two different biological mediums. The formulation of liposomes containing 159Gd and its respective controls were evaluated by in vitro cytotoxicity against tumor cells RT2. The results showed increased cytotoxic activity of approximately 1170 fold in relation to free Gd-DTPA-BMA. [Copyright &y& Elsevier]

Abstract: The gallium(III) complexes [Ga(2Am4DH)2]NO3 (1), [Ga(2Am4Me)2]NO3 (2) and [Ga(2Am4Et)2]NO3 (3) were prepared with 2-pyridineformamide thiosemicarbazone (H2Am4DH) and its N(4)-methyl (H2Am4Me) and N(4)-ethyl (H2Am4Et) derivatives. The thiosemicarbazones were cytotoxic against malignant RT2 glioblastoma cells (expressing p53 protein) with IC50 values in the 7.3–360μM range, and against malignant T98 glioblastoma cells (expressing mutant p53 protein) with IC50 values in the 3.6–143μM range. Coordination to gallium strongly increased the cytotoxic potential in complexes 2 and 3, which showed IC50 values in the 0.81–9.57μM range against RT2 cells and in the 3.6–11.30μM range against T98 cells, and were 20-fold more potent than cisplatin. All thiosemicarbazones and gallium complexes were able to induce cell death by apoptosis. [Copyright &y& Elsevier]

Abstract: Lycopene is a natural carotenoid, free radical scavenger, and presents protective effects by inhibiting oxidative DNA damage. The objective of the current study was to investigate the cytogenetic effects of a single acute and four daily gavage administrations of lycopene, and to examine possible protective effects on chromosomal damage induced by the antitumor drug cisplatin (cDDP) in rat bone marrow cells. The animals were divided into treatment groups, with three lycopene doses in the acute treatment (2, 4, and 6mg/kgb.w.), three lycopene doses in the subacute treatment (0.5, 1.0, and 1.5mg/kgb.w.) with and without cDDP (5mg/kgb.w. i.p.), and respective controls. The results indicated that lycopene is neither cytotoxic nor clastogenic when compared with the negative controls (p >0.01). cDDP-treated animals submitted to acute and subacute treatments with different lycopene doses showed a significant reduction (p <0.01) in the number of abnormal metaphases when compared with the animals treated only with cDDP. The protective effects of lycopene on cDDP-induced chromosomal damage may be attributed to its antioxidant activity. These results suggest that this carotenoid may prove useful in reducing some of the toxic effects associated with certain classes of chemotherapeutic agents. [Copyright &y& Elsevier]

• The baseline frequencies of cell damage and cell death measured by BMCyt assay were determined for Brazilian people. • Chromosomal stability in buccal cells was different among Brazilian regions but not affected by habits. • Chromosomal damage in buccal cells was influenced by age and equal for women and men. • The BMCyt assay is a good biomarker to smokers. The Buccal Micronucleus Cytome Assay (BMCyt) has become an important biomonitoring tool for assessing cytogenetic damage in many studied populations. Each laboratory applies protocols that vary according to the method of collecting and preparing samples. Besides, Brazil is a country of great territorial extensions that received immigrants from various parts of the world with different genetic backgrounds. Therefore, the present study aimed to evaluate the inter-laboratory variation in scoring the same set of slides using the more comprehensive scoring criteria, to standardize the BMCyt protocol, to observe the basal alterations in populations of different Brazilian regions and to compare it with other places around the world. Our results showed that a valuable number of laboratories participated, ten laboratories from different regions of the country, for the validation of the BMCyt in human biomonitoring studies, resulting in the 804 healthy individuals. This was possible because we observed: a range of measures needs to be considered, such as the baseline frequency of DNA damage and cell death in non-exposed individuals; age when grouped showed an influence on DNA damage, although when evaluated by group we did not see an influence; association between smoking habit and all endpoints of the BMCyt (except karyolytic cells) was evident; the basal MN frequency, in the majority of groups, follows those around the world; and the BMCyt was confirmed as a good health status biomarker. We emphasize the need for constant discussions on the parameters of cell death due to greater difficulty among the analyzers. [ABSTRACT FROM AUTHOR]

Abstract Over the last four decades of palaeoclimate research, significant emphasis has been placed on the Last Glacial Maximum (LGM) spanning 26.5–19 thousand years ago (ka), a period that saw significant (∼125 m) sea-level reductions and major ice caps adorning large parts of the Northern Hemisphere. Here, we present evidence for another major glacial period spanning 71–59 ka (Marine Isotope Stage 4: MIS4) from a well-dated marine sequence offshore South Australia. The astronomically-tuned chronology of this deep-sea core is confirmed using single-grain optically stimulated luminescence dating (OSL), providing confidence in our high-resolution age model. Our approach to the study of our MD03-2607 core has been to employ many different proxies. These are: δ18O of both planktic and benthic foraminifera for stratigraphic purposes, faunal counts of planktonic foraminifera to reconstruct the position of oceanic fronts and currents, alkenone palaeothermometry, XRF core scanning to determine the presence of aeolian dust, and εNd isotope to identify fluvial discharge over the core site. We compare our new proxy findings with other archives for mainland Australia and Tasmania. Our multi-proxy palaeoclimate reconstructions are consistent with other marine, terrestrial and cryosphere archives across the Southern Hemisphere and suggest, for the first time, that MIS 4 was almost as dramatic as the LGM. During MIS4, global sea-level was reduced by ∼100 m, glaciers across Australasia were more significant compared to the LGM, and sea-surface temperatures were much reduced. These glacial conditions uniformly peaked around 65 ka. Global comparisons show major glacial conditions and vegetation shifts elsewhere during MIS4, but many are poorly dated. The significant environmental changes taking place during this glacial period were paralleled by waves of human dispersal across Eurasia and the earliest evidence of human occupation in northern Australia at 65 ka. Highlights • MIS4 was a major glacial period between 71 and 59 ka in the Southern Hemisphere. • Glacial conditions peaked at 65 ka, sea level dropped ∼100 m and SST dropped ∼5 °C. • Glaciers In New Zealand, Australia and Papua New Guinea were more pronounced at MIS4. • Multiproxy data confirm significant oceanic frontal changes offshore South Australia. • The deuterium excess change implies higher moisture reaching Antarctica during MIS4. [ABSTRACT FROM AUTHOR]

Abstract In this study, ent -kaurenoic acid derivatives were obtained by microbial transformation methodologies and tested against breast cancer cell lines (MCF-7). A multivariate quantitative-structure activity relationship (QSAR) analysis was performed taking into account both microbial transformation derivatives and other analogues previously reported in literature to give some insight into the main features behind the cytotoxic activity displayed by kaurane-type diterpenes against MCF-7 cells. The partial least square regression (PLS) method was employed in the training set and the best PLS model was built with a factor describing 69.92% of variance and three descriptors (log P , ε HOMO and ε HOMO–1) selected by the Ordered Predictors Selection (OPS) algorithm. The QSAR model provided reasonable regression (Q 2 = 0.64, R 2 = 0.72, SEC = 0.29 and SEV = 0.33). The model was validated by leave- N -out cross-validation, y-randomization and external validation (R 2 pred = 0.89 and SEP = 0.27). The selected descriptors indicated that the activity was mainly related to electronic parameters (HOMO and HOMO-1 molecular orbital energies), as well as to log P. These findings suggest that higher activity values are directly related with both higher log P and frontier orbital energy values. The positive relationship between these orbitals and the activity suggests that the ent -kaurenoic acid analogues interaction with the target involves charge displacement, which is entirely consistent with the literature. Based on these findings, three compounds were proposed and one of them was synthesized and tested. The experimental result confirmed the activity predicted by the model. Graphical abstract According to QSAR analysis, the activity of kaurenoic acid derivatives against MCF-7 breast cancer cells is related to the log P and to the energies of the HOMO and HOMO–1. Image 1 Highlights • Kaurenoic acid derivatives interact with MCF7 cells by charge transfer mechanism. • Higher activity against MCF-7 cells is related with both log P and frontier orbitals. • Kaurenoic acid derivatives were proposed to be synthetized based on the QSAR model. [ABSTRACT FROM AUTHOR]

Fossil-bearing deposits in the Transantarctic Mountains, Antarctica indicate that, despite the cold nature of the continent’s climate, a tundra ecosystem grew during periods of ice sheet retreat in the mid to late Neogene (17–2.5 Ma), 480 km from the South Pole. To date, palaeotemperature reconstruction has been based only on biological ranges, thereby calling for a geochemical approach to understanding continental climate and environment. There is contradictory evidence in the fossil record as to whether this flora was mixed angiosperm-conifer vegetation, or whether by this point conifers had disappeared from the continent. In order to address these questions, we have analysed, for the first time in sediments of this age, plant and bacterial biomarkers in terrestrial sediments from the Transantarctic Mountains to reconstruct past temperature and vegetation during a period of East Antarctic Ice Sheet retreat. From tetraether lipids (MBT′/CBT palaeothermometer), we conclude that the mean continental summer temperature was ca. 5 °C, in agreement with previous reconstructions. This was warm enough to have allowed woody vegetation to survive and reproduce even during the austral winter. Biomarkers from vascular plants indicate a low diversity and spatially variable flora consisting of higher plants, moss and algal mats growing in microenvironments in a glacial outwash system. Abietane-type compounds were abundant in some samples, indicating that conifers, most likely Podocarpaceae, grew on the Antarctic continent well into the Neogene. This is supported by the palynological record, but not the macrofossil record for the continent, and has implications for the evolution of vegetation on Antarctica. [ABSTRACT FROM AUTHOR]

The diterpene kaurenoic acid (KA) has vasorelaxant, antimicrobial, anti-tumoural and anti-leishmanial effects. Semi-synthetic derivatives were obtained to achieve more satisfactory responses. The assessment of genotoxicity is part of the toxicological evaluation of therapeutic compound candidates. The present study investigated the cytotoxicity and genotoxicity of KA and its semi-synthetic derivatives methoxy kaurenoic acid (MKA) and kaurenol (KRN) using the CHO-K1 cell line. The cytotoxicity evaluation demonstrated that treatments with 200 and 400 μM KA reduced cellular proliferation to 36.5 and 4.43%, respectively, and that 100 and 200 μM KA reduced the survival fraction (SF) to 48.1 and 5.5%, respectively. MKA and KRN at concentrations of 400 μM reduced proliferation to 81 and 86.8%, respectively, while 100 and 200 μM KRN reduced the SF to 50%, and 200 μM MKA reduced the SF to 74%. No genotoxicity was observed for KA or MKA. However, 100 μM KRN increased the DNA damage index, as detected by comet assay, although a micronucleus assay did not confirm these data. The results demonstrated that KA and its semi-synthetic derivative MKA were not genotoxic when tested at noncytotoxic concentrations, but KRN was genotoxic at the highest concentration that was tested, as demonstrated by the comet assay. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Serjania marginata (Sapindaceae), a medicinal plant commonly found in the Brazilian Cerrado, Paraguay, Bolivia and Argentina, is also known as “cipó-uva” or “cipó-timbó”. Ethnopharmacological studies indicate that the leaves from this medicinal plant are used in folk medicine to treat gastric pain. The overall objective of this study was to evaluate the gastroprotective and healing effect of the hydroalcoholic extract obtained from S. marginata (HESM) leaves using rodent experimental models. As part of the integrative study of this medicinal plant, we also evaluated the acute toxicity, antimicrobial, antidiarrheal, (anti)mutagenic, and hemodynamic effects. Material and methods We performed a pharmacological study to test the acute toxicity and antimutagenic effect (Ames assay) of the HESM. The HESM was tested against different necrosis-promoting agents and experimental manipulations, such as absolute ethanol, cysteamine, pyloric ligature, and ischemia–reperfusion (I/R) injury. The gastroprotective effect of the HESM was assessed by analyzing the gastric juice (volume, pH, total acidity) and the mucus in the gastric mucosa from rats. We assessed the levels of NO, sulfhydryl compounds, PGE 2 , vanilloid receptor, glutathione (GSH), and malondialdehyde (MDA), as well as the myeloperoxidase (MPO) activity. The gastric healing effects of the HESM were evaluated during 7 or 14 days of treatment. The intestinal motility, antidiarrheal action, and antibacterial effects (microdilution methods) of the HESM were also evaluated. Results The phytochemical analysis of the HESM revealed the presence of saponins, flavonoid glycosides, and tannins. The extract exhibited no sign of acute toxicity or mutagenic effect in vitro . In contrast, this extract exhibited a protective effect against the mutagenic action of direct- and indirect-acting mutagens. Only the oral administration of HESM (250 mg/kg) significantly decreased the severity of gastric damage induced by ethanol (60.13%) and I/R (58.31%). The HESM exerts its gastroprotective effects by decreasing the MPO and MDA activities in the gastric tissue and by increasing the amount of adherent mucus covering the gastric mucosa. In vitro , the extract also displayed evident antimicrobial effects against Helicobacter pylori . However, the preventive effect of the HESM was not accompanied by an ulcer-healing effect. The treatment with HESM (14 days) significantly increased gastric lesions in 99% of the tested animals compared with the control group. This result represents a highly relevant piece of evidence that should resonate as an alert against the chronic use of this medicinal plant as an antiulcer in folk medicine. Conclusions Despite the anti- H. pylori and gastroprotective actions of S. marginata in experimental models, the gastric injuries aggravation induced after chronic treatment with the HESM argues against the use of this plant species in folk medicine. [ABSTRACT FROM AUTHOR]

The use of poly( l -lactic acid) (PLA) has been considered an important alternative for medical devices once this polyester presents biomechanical, optical and biodegradable properties. Moreover, the use of PLA results in less inflammatory reactions and more recently it has been proposed its application in drug delivery systems. Genotoxicological evaluations are considered part of the battery assays in toxicological analysis. Considering the wide applications of PLA, the present work evaluated the potential cytotoxic and genotoxic effects of PLA in CHO-K1 cells, as well as its physicochemical properties. No cytotoxic effects of PLA were detected by colorimetric tetrazolium assay (XTT) analysis, and the clonogenic survival assay showed that PLA did not disrupt the replicative cell homeostasis, neither exhibited genotoxic effects as evidenced by comet and micronucleus assays. Thermogravimetric properties of PLA were not altered after contact with cells and this film exhibited ability in absorb and release Europium(III) complex. All these data suggest genotoxicological safety of PLA for further applications in drug delivery systems. [ABSTRACT FROM AUTHOR]

Highlights: [•] Australian core top sediments from the sediment/water interface were obtained. [•] Sea temperature was compared with World Ocean Atlas 2009 using three biomarker proxies for the same samples. [•] and LDI proxies related to mean annual sea surface temperature. [•] proxy reflected integrated 0–200m sea temperature. [Copyright &y& Elsevier]

Abstract: N 4-Phenyl 2-acetylpyridine thiosemicarbazone (H2Ac4Ph; N-(phenyl)-2-(1-(pyridin-2-yl)ethylidene)hydrazinecarbothioamide) and its N 4-ortho-, -meta- and -para-fluorophenyl (H2Ac4oFPh, H2Ac4mFPh, H2Ac4pFPh), N 4-ortho-, -meta- and -para-chlorophenyl (H2Ac4oClPh, H2Ac4mClPh, H2Ac4pClPh), N 4-ortho-, -meta- and -para-iodophenyl (H2Ac4oIPh, H2Ac4mIPh, H2Ac4pIPh) and N 4-ortho-, -meta- and -para-nitrophenyl (H2Ac4oNO2Ph, H2Ac4mNO2Ph, H2Ac4pNO2Ph) derivatives were assayed for their cytotoxicity against human malignant breast (MCF-7) and glioma (T98G and U87) cells. The compounds were highly cytotoxic against the three cell lineages (IC50: MCF-7, 52–0.16nM; T98G, 140–1.0nM; U87, 160–1.4 nM). All tested thiosemicarbazones were more cytotoxic than etoposide and did not present any haemolytic activity at up to 10−5 M. The compounds were able to induce programmed cell death. H2Ac4pClPh partially inhibited tubulin assembly at high concentrations and induced cellular microtubule disorganization. [Copyright &y& Elsevier]

Abstract: 2-Acetylpyridine-phenylhydrazone (H2AcPh), its para-chlorophenylhydrazone (H2AcpClPh) and para-nitrophenylhydrazone (H2AcpNO2Ph) analogues, the corresponding 2-benzoylpyridine-derived hydrazones (H2BzPh, H2BzpClPh and H2BzpNO2Ph) and their gallium(III) complexes were assayed for their cytotoxic activity against U87 (expressing wild-type p53 protein) and T98 (expressing mutant p53 protein) glioma cells. IC50 values against both glioma cells and against the MRC5 (human fetal lung fibroblast) lineage were obtained for the hydrazones, but not for their gallium(III) complexes, due to their low solubility. Hydrazones were highly cytotoxic at nanomolar doses against U87 and T98 cells. The therapeutic indexes (TI = IC50MRC5/IC50glioma) were 2-660 for T98 cells and 28-5000 for U87 cells, indicating that the studied hydrazones could be good antitumor drug candidates to treat brain tumors. [Copyright &y& Elsevier]

Abstract: 2-Acetylpyridine N(4)-phenyl thiosemicarbazone (H2Ac4Ph), and its N(4)-ortho-tolyl (H2Ac4oT), N(4)-meta-tolyl (H2Ac4mT), N(4)-para-tolyl (H2Ac4pT), N(4)-ortho-chlorophenyl (H2Ac4oClPh), N(4)-meta-chlorophenyl (H2Ac4mClPh) and N(4)-para-chlorophenyl (H2Ac4pClPh) derivatives were assayed for their cytotoxicity against RT2 (expressing p53 protein) and against T98 (expressing mutant p53 protein) glioma cells. The compounds were highly cytotoxic against RT2 (IC50 =24–1.4nM) and T98 cells (IC50 =50–1.0nM). IC50 for cisplatin=5 (RT2) and 17μM (T98). The thiosemicarbazones presented haemolytic activity with IC50 >10−3M, indicating a very good therapeutic index. SAR studies suggested that stereo properties are critical to define the potential activity of the studied compounds against the RT2 cell line, while electronic properties seem to be important for interaction with the biological target in T98 cells. [ABSTRACT FROM AUTHOR]