Hyperhomocysteinemia in Renal Transplantation: Preliminary Results

Cardiovascular disease (CVD) is a major cause of morbidity and mortality after renal transplantation (RT).[1] and [2] The excess risk of CVD in RT is due in part to a higher prevalence of established atherosclerotic risk factors, including hypertension, dyslipidemia, diabetes, obesity, and physical inactivity.[1] and [2] However, some renal-related risk factors like immunosuppressive medication and residual renal insufficiency also contribute to this excess CVD risk and may complicate the management of dyslipidemia and hypertension in this population.[1] and [2] Accordingly, there is a compelling need to identify and safely manage other putative CVD risk factors among RT patients. Elevated plasma homocysteine is emerging as an important risk factor for cardiovascular disease in general populations.[3] and 4 R Clarke, L Daly and K Robinson et al., N Engl J Med 324 (1991), p. 1149. View Record in Scopus | Cited By in Scopus (1372)[4] Some studies have demonstrated that hyperhomocysteinemia is present in patients with impaired renal function and is associated with CVD.[5], [6] and [7] Only a small number of studies are available on the prevalence and determinants of hyperhomocysteinemia in renal transplant recipients.[8], [9], [10], [11], [12], [13], [14] and [15] We undertook this study to 1. estimate the prevalence of hyperhomocysteinemia in renal transplant recipients; 2. examine the relationships between plasma total homocysteine (tHcy) and its metabolic determinants vitamin B6, vitamin B12, and folic acid; and 3. identify other determinants of tHcy

Delivering amoxicillin at the infection site-a rational design through lipid nanoparticles

Purpose: Amoxicillin is a commonly used antibiotic, although degraded by the acidic pH of the stomach. This is an important limitation for the treatment of Helicobacter pylori infections. The purpose of this work was to encapsulate amoxicillin in lipid nanoparticles, increasing the retention time at the site of infection (gastric mucosa), while protecting the drug from the harsh conditions of the stomach lumen. Materials and methods: The nanoparticles were produced by the double emulsion technique and optimized by a three-level Box-Behnken design. Tween 80 and linolenic acid were used as potential therapeutic adjuvants and dioleoylphosphatidylethanolamine as a targeting agent to Helicobacter pylori. Nanoparticles were characterized regarding their physico-chemical features, their storage stability, and their usability for oral administration (assessment of in vitro release, in vitro cell viability, permeability, and interaction with mucins). Results: The nanoparticles were stable for at least 6 months at 4°C. In vitro release studies revealed a high resistance to harsh conditions, including acidic pH and physiologic temperature. The nanoparticles have a low cytotoxicity effect in both fibroblasts and gastric cell lines, and they have the potential to be retained at the gastric mucosa. Conclusion: Overall, the designed formulations present suitable physico-chemical features for being henceforward used by oral administration to treat Helicobacter pylori infections.DLC, RMP, TS, and CN are thankful to Fundação para a Ciência e Tecnologia (FCT) for the PhD Grant (PD/ BD/105957/2014), Research Grant (PD/BI/128326/2017), post-doctorate grant (SFRH/BPD/103113/2014), and Investigator Grant (IF/00293/2015), respectively. This work was supported by FCT through the FCT PhD Programmes and by Programa Operacional Capital Humano (POCH), specifically by the BiotechHealth Programe (Doctoral Programme on Cellular and Molecular Biotechnology Applied to Health Sciences). The authors are also grateful to Dr Rui Fernandes (Histology and Electron Microscopy Service – Instituto de Investigação e Inovação em Saúde, Universidade do Porto) for the expertise and technical assistance with transmission electron microscopy and to Manuela Barros for administrative and technical support. The authors thank the financial support under Program PT2020 (UID/QUI/50006/2019). SACL and BS thanks Operação NORTE-01-0145-FEDER-000011 and NORTE-01-0145-FEDER-000012, respectively, for their Investigator contract

ParaMT: a Paraphraser for Machine Translation

In this paper we present ParaMT, a bilingual/multilingual paraphraser to be applied in machine translation. We select paraphrases of support verb constructions and use the NooJ linguistic environment to formalize and generate translation equivalences through the use of dictionary and local grammars with syntactic and semantic content. Our research shows that linguistic paraphrasal knowledge constitutes a key element in conversion of source language into controlled language text that presents more successful translation result

Impact of splenic artery ligation after major hepatectomy on liver function, regeneration and viability

It was reported that prevention of acute portal overpressure in small-for-size livers by inflow modulation results in a better postoperative outcome. The aim is to investigate the impact of portal blood flow reduction by splenic artery ligation after major hepatectomy in a murine model. Forty-eight rats were subjected to an 85% hepatectomy or 85% hepatectomy and splenic artery ligation. Both groups were evaluated at 24, 48, 72 and 120 post-operative hours: liver function, regeneration and viability. All methods and experiments were carried out in accordance with Coimbra University guidelines. Splenic artery ligation produces viability increase after 24 h, induces a relative decrease in oxidative stress during the first 48 hours, allows antioxidant capacity increment after 24 h, which is reflected in a decrease of half-time normalized liver curve at 48 h and at 72 h and in an increase of mitotic index between 48 h and 72 h. Splenic artery ligation combined with 85% hepatectomy in a murine model, allows portal inflow modulation, promoting an increase in hepatocellular viability and regeneration, without impairing the function, probably by inducing a less marked elevation of oxidative stress at first 48 hours

Endometrial Cancer Spheres Show Cancer Stem Cells Phenotype and Preference for Oxidative Metabolism

This study aimed to characterize endometrial cancer regarding cancer stem cells (CSC) markers, regulatory and differentiation pathways, tumorigenicity and glucose metabolism. Endometrial cancer cell line ECC1 was submitted to sphere forming protocols. The first spheres generation (ES1) was cultured in adherent conditions (G1). This procedure was repeated and was obtained generations of spheres (ES1, ES2 and ES3) and spheres-derived cells in adherent conditions (G1, G2 and G3). Populations were characterized regarding CD133, CD24, CD44, aldehyde dehydrogenase (ALDH), hormonal receptors, HER2, P53 and β-catenin, fluorine-18 fluorodeoxyglucose ([18F]FDG) uptake and metabolism by NMR spectroscopy. An heterotopic model evaluated differential tumor growth. The spheres self-renewal was higher in ES3. The putative CSC markers CD133, CD44 and ALDH expression were higher in spheres. The expression of estrogen receptor (ER)α and P53 decreased in spheres, ERβ and progesterone receptor had no significant changes and β-catenin showed a tendency to increase. There was a higher 18F-FDG uptake in spheres, which also showed a lower lactate production and an oxidative cytosol status. The tumorigenesis in vivo showed an earlier growth of tumours derived from ES3. Endometrial spheres presented self-renewal and differentiation capacity, expressed CSC markers and an undifferentiated phenotype, showing preference for oxidative metabolism.info:eu-repo/semantics/publishedVersio

Proinflammatory and endothelial activation profiles in hospitalized COVID-19 patients: impact of arterial hypertension and previous treatment with renin-angiotensin-aldosterone inhibitors

n/

Hierarchical structured and programmed vehicles deliver drugs locally to inflamed sites of intestine

Orally administrable drug delivery vehicles are developed to manage incurable inflammatory bowel disease (IBD), however, their therapeutic outcomes are compromised by the side effects of systemic drug exposure. Herein, we use hyaluronic acid functionalized porous silicon nanoparticle to bridge enzyme-responsive hydrogel and pH-responsive polymer, generating a hierarchical structured (nano-in-nano-in-micro) vehicle with programmed properties to fully and sequentially overcome the multiple obstacles for efficiently delivering drugs locally to inflamed sites of intestine. After oral administration, the pH-responsive matrix protects the embedded hybrid nanoparticles containing drug loaded hydrogels against the spatially variable physiological environments of the gastrointestinal tract until they reach the inflamed sites of intestine, preventing premature drug release. The negatively charged hybrid nanoparticles selectively target the inflamed sites of intestine, and gradually release drug in response to the microenvironment of inflamed intestine. Overall, the developed hierarchical structured and programmed vehicles load, protect, transport and release drugs locally to inflamed sites of intestine, contributing to superior therapeutic outcomes. Such strategy could also inspire the development of numerous hierarchical structured vehicles by other porous nanoparticles and stimuli-responsive materials for the local delivery of various drugs to treat plenty of inflammatory gastrointestinal diseases, including IBD, gastrointestinal cancers and viral infections.Peer reviewe

Evaluation of urinary cysteinyl leukotrienes as biomarkers of severity and putative therapeutic targets in COVID-19 patients

Background Cysteinyl leukotrienes (CysLT) are potent inflammation-promoting mediators, but remain scarcely explored in COVID-19. We evaluated urinary CysLT (U-CysLT) relationship with disease severity and their usefulness for prognostication in hospitalized COVID-19 patients. The impact on U-CysLT of veno-venous extracorporeal membrane oxygenation (VV-ECMO) and of comorbidities such as hypertension and obesity was also assessed. Methods Blood and spot urine were collected in severe (n = 26), critically ill (n = 17) and critically ill on VV-ECMO (n = 17) patients with COVID-19 at days 1-2 (admission), 3-4, 5-8 and weekly thereafter, and in controls (n = 23) at a single time point. U-CysLT were measured by ELISA. Routine markers, prognostic scores and outcomes were also evaluated. Results U-CysLT did not differ between groups at admission, but significantly increased along hospitalization only in critical groups, being markedly higher in VV-ECMO patients, especially in hypertensives. U-CysLT values during the first week were positively associated with ICU and total hospital length of stay in critical groups and showed acceptable area under curve (AUC) for prediction of 30-day mortality (AUC: 0.734, p = 0.001) among all patients. Conclusions U-CysLT increase during hospitalization in critical COVID-19 patients, especially in hypertensives on VV-ECMO. U-CysLT association with severe outcomes suggests their usefulness for prognostication and as therapeutic targets.This work was supported by a RESEARCH 4 COVID-19 grant (project 519, reference number: 613690173) from FCT-Fundacao para a Ciencia e a Tecnologia (special support for rapid implementation projects for innovative response solutions to COVID-9 pandemic). CS-P is a recipient of a Ph.D. fellowship from FCT and MedInUP (UI/BD/150816/2020). P-PT was supported by a research contract within the scope of the RIFF-HEART project funded by FEDER via COMPETE, Portugal 2020-Operational Programme for Competitiveness and Internationalization (POCI) (POCI-01-0145-FEDER-032188) and by FCT (PTDC/MEC-CAR/32188/2017). Open access funding provided by FCT|FCCN (b-on)

Scaffold Vaccines for Generating Robust and Tunable Antibody Responses

Traditional bolus vaccines often fail to sustain robust adaptive immune responses, typically requiring multiple booster shots for optimal efficacy. Additionally, these provide few opportunities to control the resulting subclasses of antibodies produced, which can mediate effector functions relevant to distinct disease settings. Here, it is found that three scaffold-based vaccines, fabricated from poly(lactide-co-glycolide) (PLG), mesoporous silica rods, and alginate cryogels, induce robust, long-term antibody responses to a model peptide antigen gonadotropin-releasing hormone with single-shot immunization. Compared to a bolus vaccine, PLG vaccines prolong germinal center formation and T follicular helper cell responses. Altering the presentation and release of the adjuvant (cytosine-guanosine oligodeoxynucleotide, CpG) tunes the resulting IgG subclasses. Further, PLG vaccines elicit strong humoral responses against disease-associated antigens HER2 peptide and pathogenic E. coli, protecting mice against E. coli challenge more effectively than a bolus vaccine. Scaffold-based vaccines may thus enable potent, durable and versatile humoral immune responses against disease

Serra do Navio, Guiana Shield lowland area, Brazil: a region with high diversity of Squamata

The Guiana Region is the area bordered by the Orinoco and Negro rivers to the west, by the Amazonas River to the south and by the Atlantic Ocean to the north and east. This area is a biogeographic unit known as the Guiana Shield, with a variety of landscapes. Located in the extreme north of Brazil, in the Guiana Shield lowlands, the state of Amapá presents great diversity of habitats. In this study we provide composition and diversity data of the Squamata from Serra do Navio (SN) region, in the northeastern part of the state of Amapá, Brazil, a lowland area of the Guiana Shield. The species list was based on data obtained from herpetological collections and collection expeditions carried out at 10 sites in the municipalities of Pedra Branca do Amapari and Serra do Navio. We consider literature data from 14 sites and SN data to compare the composition of herpetofauna between the lowland and highland areas in the Brazilian Amazon.We recorded 95 species, including 57 snakes, 36 lizards, and two species of amphisbaenians. Atractus aboiporu, A. trefauti, and Erythrolamprus rochai were described from the data collected in this study. The Squamata community of SN consists mainly of diurnal lizards and nocturnal snakes, with terrestrial and cryptozoic habits, present in pristine and altered environments. The most abundant species of lizard and snake were Loxopholis guianense and Atractus latifrons, respectively. The SN region has 17 exclusive Squamata species, with a fauna similar to the Tumucumaque Mountains and northern Pará sites, geographically closer regions with similar altitudes.Asociación Herpetológica Argentin