Hepatic mitochondrial content in malondialdehyde may be a marker of sea lamprey contact with atrazine

The atrazine attracts special attention as pollutant because of itspersistence in the aquatic environment. Although this herbicide has been studied in teleost, its toxicity in the sea lamprey, Petromyzon marinus is still poorly understood. Oxidative stress may occur if chemical pollutants contribute to block the capacity of mitochondria to generate ATP with continuous production of reactive oxygen species (ROS), disturbing the success of P. marinus seawater acclimation. So, the aim of this study was to evaluate how atrazine influences the malondialdehyde (MDA), glutathione (GSH) and glutathione disulfide (GSSG) contents of gills and liver mitochondria of juveniles from Lima river basin, Portugal during salt acclimation. Sampling occurred at the beginning of the P. marinus downstream migration. The sampled juveniles were transported alive to the laboratory and maintained in 200 l tanks with LSS 8 life support system. Two groups of 40 specimens were hold in tanks with 50 or 100 lg/l atrazine, during 30 days. The salinity was gradually increased from 0 to 35 psu,following a three step procedure during a 30 days period. The control group was maintained in freshwater without atrazine. Mitochondria obtained by centrifugation at 15000 g, 30 min, 4°C, of tissues homogenates prepared in 50 mM Tris-HCl pH 7.5 buffer were used in determination of ROS, MDA, GSH and GSSG by fluorescence. The statistical analysis were performed by ANOVA I and Duncan (p < 0.05), using SPSS 22 for Windows.The results showed that in P. marinus juveniles, no significant changes in the markers of oxidative stress and cell damages were detected in the mitochondrial gills. Nevertheless, in the animals exposed to 50 lg/l atrazine the content in glutathione and GSSG increased. A similar pattern of stress markers was detected in hepatic mitochondria. However, in the presence of atrazine, the MDA level of the mitochondria of liver increased threefold in the animals during salt acclimation. The high level of mitochondrial damages, detected in the hepatic mitochondria of macrophthalmia treated with atrazine, suggests that herbicide exposure caused metabolic failures which can disturb the adaptation of these specimens to the oceanic feeding phase. The hepatic mitochondrial MDA levels of P. marinus, may eventually detect sea lamprey contact with chlorine herbicides

Successful management of bilateral orbital metastases from invasive lobular breast cancer with abemaciclib and letrozole: a case report and literature review

Breast cancer is a significant global health concern, contributing to substantial morbidity and mortality among women. Hormone receptor-positive (HR+)/HER2- negative (HER2-) breast cancer constitutes a considerable proportion of cases, and significant advancements have been made in its management. CDK4/6 inhibitors (CDK4/6is) are a new targeted therapy that has demonstrated efficacy in adjuvant, advanced and metastatic settings. The propensity of lobular breast carcinomas for estrogen-rich sites, such as periocular tissues and orbital fat, may explain their tendency for orbital metastases. Current treatment strategies for these cases are predominantly palliative, and the prognosis remains poor. This article presents a unique case of a 51-year-old female with progressive right periorbital edema, pain, and limited ocular motility. An imaging work-up showed bilateral intra and extraconal orbital infiltration, which was biopsied. The histopathologic analysis disclosed mild chronic inflammatory infiltrate with thickened fibrous tissue and moderately differentiated lobular carcinoma cells, positive for GATA3 and CK7 markers, with 100% of tumor nuclei expressing estrogen receptors (ER+). A systemic evaluation showed a multicentric nodular formation in both breasts. Further diagnostic assessments unveiled an HR+/HER2- bilateral lobular breast carcinoma with synchronous bilateral orbital metastases. Systemic treatment was initiated with abemaciclib 150mg twice daily and letrozole 2.5mg once a day. However, this regimen was interrupted due to toxicity. After two weeks, treatment was resumed with a reduced abemaciclib dose (100mg twice daily) alongside letrozole, with a reasonable tolerance. Nearly two years after the initial diagnosis of inoperable metastatic cancer, the patient remains on the same systemic treatment regimen with no signs of invasive disease. This case report is the first of a patientpresenting with bilateral orbital metastases from bilateral lobular breast cancer, showing an impressive and sustained response to a first-line treatment regimen combining abemaciclib and letrozole. A literature review on bilateral orbital metastases from breast cancer is also presented.info:eu-repo/semantics/publishedVersio

Can the mitochondrial malondialdehyde content be an useful tool to distinguish ecological quality of Petromyzon marinus habitat?

The sea lamprey is an anadromous species that migrates twice during its life cycle between freshwater and seawater. Microphagous larvae generally spend 4–5 years burrowed in the substrate of rivers and streams before undergoing metamorphosis that ends with the beginning of the juvenile trophic migration. Once metamorphosis is complete, sea lamprey juvenile downstream migrants are fully tolerant to 35 PSU seawater. Pollution resulting from industrial effluents may disturb the seawater acclimatization causing oxidative damages, and ultimately may lead to a decrease of sea lamprey population. The aim of this study was to compare salt acclimation of sea lamprey juveniles captured in river basins with different levels of aquatic pollution, using mitochondrial glutathione and malondialdehyde of gills and liver as markers of physiological stress and cell damages. The results showed that juveniles from Lima basin exhibited the highest levels of mitochondrial malondialdehyde in gills, even though significant changes in the stress markers of mitochondrial gills of all animals subject to salt acclimation were not detected. In addition, an increase in the oxidative damages of hepatic mitochondria of macrophthalmia from Vouga basin suggests the occurrence of metabolic failures with the potential to disturb the capacity to adaptation to the marine environment

Leveraging vectored vaccine candidates manufacturing to GMP compatible bioprocesse

Background Vectored vaccines are very efficient in the in vivo delivery of antigens either in the form of antigen protein and peptides or genetic material. The bioprocess of vectored vaccines poses however several challenge since the viral particles to be effective must maintain their infectivity. Lentiviral and adenoviral vectors are among the particles more used in the treatment of cancer diseases modulating the immune system. Both viral vectors are currently produced in transient upstream process. While the adenoviral vectors are produced at high titers the lentiviral vector upstream process still requires further improvement. The non-lytic nature of lentivirus enables the design of stable cell lines which may improve its yields through perfusion and longer term productions, reducing costs. The application of novel methods for the downstream processing such as continuous purification will contribute to increase the yield and lower the overall cost of the manufacturing processes. Experimental approach At the upstream process, many of the challenges lentiviral bioproducts present in its manufacturing are related to the apoptosis-leading cytotoxicity of some of the vector components. Supported on our long track experience and enabling tools developed for gammaretrovirus manufacturing, we undertook the challenge of establishing a constitutive stable lentiviral producer cell line. To address this challenge we proposed to eliminate or reduce the cytotoxicity of the lentiviral vector expression components. At the downstream process lentiviral vectors face the challenges common to retroviridae family of vectors namely short half-lives at room temperature, sensitivity to pH variations and salt concentrations, and shear stress. The purification strategy developed was designed to be based on disposable and easily scalable technologies. A final concentration achieving 108 TU mL-1 was targeted since the concentration step itself allows to reduce the burden on process and improve the transduction efficiency. To address the high doses requirements we will report an improved oncolytic adenovirus purification process for phase I and II clinical trials and present a case on the use of Polysorb 20 as a replacement for Triton X-100 during cell lysis. Product recovery, potency, purity and the effect of manufacturing holding points will be discussed. Results and discussion A lentiviral producer cell line constitutively producing titers above 106 TU.mL-1.day-1 was established. The cell line showed to be stable, consistently maintaining vector productivity over one month in the absence of antibiotics. At the bioreaction process it was possible to maintain the cells continuously producing over 10 days. At downstream we implemented scalable protocols for lentiviral and adenoviral vectors that is easy to transfer to GMP environment, combining microfiltration, anion-exchange, and ultrafiltration membranes technologies toward maximization of infectious virus recovery, allowing generation of clinical-grade viral vectors without the need for cleaning validation in a cost-effective manner. Herein we will present and discuss the challenges on the biomanufacturing of lentiviral as well as adenoviral virus, the strategies and novel technologies to be adopted in order to enable a faster development of novel vectored vaccine candidates focusing on several case studies, supported by process technology innovation

Effect of the dispersion state of minerals on the properties of cellulose nanofiber-based composite films

The dispersion state and the efficiency of the mixture of the different components in a composite film have an important impact on its mechanical and optical properties. In the present work, the impacts of different dispersion treatments on the disaggregation state of fibrous clay particles in water, and on the properties of related cellulose nanofiber (CNF)-based composite films, were evaluated. X-ray diffraction studies, performed on samples of sepiolite and palygorskite, revealed only minor changes in the diffraction pattern when the minerals were subjected to ultrasonic treatment, with or without the addition of different chemical dispersing agents. Conversely, microscopic studies revealed important differences in the dispersion state of the samples, induced by the addition of the different dispersants, showing an improvement in the disaggregation of the mineral crystals. The composite films prepared with sepiolite (and carboxymethylcellulose, as chemical dispersant) dispersed using ultrasonic treatment, and different types of CNF, showed improved optical and mechanical properties when compared with composites of the same counterparts prepared with sepiolite dispersed using a high-speed shear disperser.info:eu-repo/semantics/publishedVersio

Structure characterization and mechanism of growth of PbTe nanocrystals embedded in a silicate glass

A nanocomposite consisting of PbTe nanocrystals embedded in a silicate glass was studied by small-angle x-ray scattering during the early stage of isothermal annealing at 793 K. A theoretical function based on a model of spherical PbTe nanocrystals surrounded by a Pb and Te depleted shell fits well to all experimental curves. The time dependences of the nanocrystal radius and size of the depleted shell agree with the prediction of the theory of nucleation and growth by the classical mechanism of atomic diffusion.892

Composition and evaluation of the lethality of Lippia gracilis essential oil to adults of Biomphalaria glabrata and larvae of Artemia salina

Lippia gracilis essential oil (LGEO) was evaluated for its molluscicidal activity against Biomphalaria glabrata and toxicity to brine shrimps (Artemia salina). L. gracilis was collected from the city Tomar do Gerú- Sergipe, Brazil. The LGEO were characterized by gas chromatography-mass spectrometry (GC/MS). The values of LC10, LC50 and LC90 were respectively 36.9, 62.2 and 82.8 ppm for B. glabrata and 19.6, 23.6 and 26.1 ppm for A. salina. GC/MS analysis showed a total volatile content of 98.6% in the LGEO. The major components were identified as thymol (24.0%), p-cymene (15.9%), methyl-thymol (11.7%), γ-terpinene (10.9%) and β-caryophyllene (7.8%).Keywords: Chemical composition, Lippia species, molluscicidal activity, Verbenacea

Five-Year Outcome in Stroke Patients Submitted to Thrombolysis

BACKGROUND AND PURPOSE: Little is known on long-term follow-up after thrombolysis in ischemic stroke patients because the majority of studies evaluated outcome at 3 to 12 months. We aimed to assess 5-year outcome after intravenous thrombolysis (IVT). METHODS: Cohort study based on the prospective registry of all consecutive ischemic stroke patients submitted to IVT in our Stroke Unit. Five-year outcome, including living settings, functional outcome, stroke recurrence, and mortality, was ascertained by telephonic interviews and additional review of clinical records. Multivariate analyses were performed to identify predictors of outcome and mortality. Excellent outcome was defined as modified Rankin scale 0 to 1. RESULTS: Five-year outcome was available for 155/164 patients submitted to IVT. At 5 years, 32.9% of patients had an excellent outcome (95% confidence interval (CI) =25.5-43.3) and mortality was 43.9% (95%CI=36.1-51.7). Increasing age (odds ratio =0.93, 95% CI =0.90-0.97) and increasing National Institute of Health Stroke Scale (NIHSS) 24 h after thrombolysis (odds ratio =0.81, 95% CI =0.74-0.90) were independently associated with a lower likelihood of an excellent 5-year outcome. Age (hazards ratio =1.07, 95% CI =1.03-1.11) and excellent functional outcome 3 months after thrombolysis (hazards ratio =0.28, 95%CI=0.12-0.66) were independently associated with mortality during follow-up. CONCLUSIONS: One third of ischemic stroke patients have excellent 5-year outcome after IVT. Younger age, lower NIHSS 24 h after IVT, and excellent 3-month functional outcome are independent predictors of excellent 5-year outcome

Orolingual angioedema after thrombolysis is not associated with insular cortex ischemia on pre-thrombolysis CT

Orolingual angioedema (OA) is a well known early complication of treatment with alteplase in ischemic stroke patients. Our aim was to study risk factors for OA in these patients, namely insular cortex ischemia

L\'evy flights of photons in hot atomic vapours

Properties of random and fluctuating systems are often studied through the use of Gaussian distributions. However, in a number of situations, rare events have drastic consequences, which can not be explained by Gaussian statistics. Considerable efforts have thus been devoted to the study of non Gaussian fluctuations such as L\'evy statistics, generalizing the standard description of random walks. Unfortunately only macroscopic signatures, obtained by averaging over many random steps, are usually observed in physical systems. We present experimental results investigating the elementary process of anomalous diffusion of photons in hot atomic vapours. We measure the step size distribution of the random walk and show that it follows a power law characteristic of L\'evy flights.Comment: This final version is identical to the one published in Nature Physic