In Vitro Toxicity of Asparagus Saponins in Distinct Multidrug-Resistant Colon Cancer Cells

Colorectal cancer is the third most common cancer in the world. Many efforts have focused on finding natural molecules with potential chemo-preventive activity due to their low toxicity compared to synthetic drugs. However, comprehensive information on the bioactive fractions and components is still missing. In this study, we developed a method for the quantitative separation and isolation of saponins from asparagus genotypes consisting of an adsorption chromatography and subsequent liquid chromatographic separation on a reversed-phase column. The saponins isolated were tested for their cytotoxic activity against human colon cancer cell lines, which could develop cross-resistance to a wide variety of chemotherapeutic drugs. Our results showed that Huétor-Tájar asparagus saponins (HTSAP), mainly protodioscin and HTSAP-10 have higher cytotoxic activity than HTSAP-1, HTSAP-6, and HTSAP-8. This study links the potential anticancer effect of asparagus to specific saponins and unveils the triguero Huétor-Tájar asparagus as a nutraceutical particularly in colon cancer therapiesMinisterio de Economía y Competitividad JCI-2012-1308

Saponins from edible spears of wild asparagus inhibit AKT, p70S6K, and ERK signalling, and induce apoptosis through G0/G1 cell cycle arrest in human colon cancer HCT-116 cells

41 Páginas, 6 Figuras, 1 TablaThe effects of steroidal saponins from edible spears of wild triguero Huetor-Tajar asparagus on some of the oncogenic molecular pathways that are affected in human colon cancer cells were investigated. Reverse-phase chromatography and a new HPLC-MS method were used to respectively isolate and analyse the composition of the steroidal saponins. They were resistant to simulated digestion and, when in contact with HTC-116 human colon carcinoma cells, interfered with extracellular signal-regulated kinase (ERK), S6 kinase (p70S6K, mTOR), and RAC-alpha serine/threonine-protein kinase (AKT) pathways by a downregulation of these proteins. The expressions of cyclins D, E, and A were also decreased, leading to G0/G1 cell cycle arrest. In addition, these steroidal saponins induced typical features of apoptosis by the promotion of caspase-3 activity, poly(ADP-ribose) polymerase 1 (PARP-1) cleavage, and DNA fragmentation. These results offer potential dietary intervention strategy against human colon cancer cells.This study was supported by grants AGL2011-29632 and AGL2011-29008 funded by MICINN. S.L. acknowledges financial support from the Spanish MINECO (JCI-2012-13084, Juan de la Cierva) and the Spanish Research Council (CSIC)/JAE-doc Program (JAEDOC089), a contract cofounded by the European Social Fund (ESF).Peer reviewe

Screening for selective anticancer activity of plants from Grazalema Natural Park, Spain

Since plants are an important source of anticancer drugs, we have carried out a random screening for selective anticancer activity of 57 extracts from 45 plants collected in Grazalema Natural Park, an area in the South of Spain of high plant diversity and endemism. Using lung cancer cells (A549) and lung non-malignant cells (MRC-5), we found that several extracts were more cytotoxic and selective against the cancer cells than the standard anticancer agent cisplatin. Five active extracts were further tested in cancer and normal cell lines from other tissues, including three skin cell lines with increasing degree of malignancy. An extract from the leaves of Daphne laureola L. (Thymelaeaceae) showed a striking potency and selectivity on lung cancer cells and leukemia cells; the IC50 values against these cancer cells were approximately 10,000-fold lower than against the normal cells. Daphnane-type diterpene orthoesters may be responsible for this highly selective anticancer activity

Position statement on infection screening, prophylaxis, and vaccination in pediatric patients with rheumatic diseases and immunosuppressive therapies, part 2: infection prophylaxis

This study aims to provide practical recommendations on prophylaxis for infection in pediatric patients with immune-mediated rheumatic diseases receiving/scheduled to receive immunosuppressive therapy. A qualitative approach was applied. A narrative literature review was performed via Medline. Primary searches were conducted using MeSH terms and free text to identify articles that analyzed data on infections and vaccinations in pediatric patients with immune-mediated rheumatic diseases receiving immunosuppressive therapy. The results were presented and discussed in a nominal group meeting comprising a committee of 12 pediatric rheumatologists from the Prevention and Treatment of Infections Working Group of the Spanish Society of Pediatric Rheumatology. Several recommendations were generated. A consensus procedure was implemented via a Delphi process that was extended to members of the Spanish Society of Pediatric Rheumatology and the Vaccine Advisory Committee of the Spanish Association of Pediatrics. Participants produced a score ranging from 0 (completely disagree) to 10 (completely agree). Agreement was considered to have been reached if at least 70% of participants voted ≥ 7. The literature review included more than 400 articles. Overall, 63 recommendations were generated (23 on infection prophylaxis) and voted by 59 pediatric rheumatologists and other pediatric specialists, all of whom achieved the pre-established level of agreement. The recommendations on prophylaxis of infection cover vaccination and prophylaxis against varicella zoster virus, tuberculosis, Pneumocystis jiroveccii, and invasive fungal infections in pediatric patients with immune-mediated rheumatic diseases receiving/scheduled to receive immunosuppressive therapy. Conclusion: Based on current evidence and a Delphi process, we provided consensus and updated recommendations on prophylaxis and treatment of infections to guide those caring for pediatric rheumatology patients.Funding for open access charge: Universidad de Málaga/CBU

Screening for selective anticancer activity of 65 extracts of plants collected in Western Andalusia, Spain

Finding cytotoxic drugs with a high selectivity towards cancer cells is crucial to improve the low survival rates of patients diagnosed with metastatic cancers. Since plants are an important source of anticancer drugs, we have screened 65 extracts from 45 plants collected in several areas of Western Andalusia (Spain) for cytotoxic activity on lung cancer cells versus lung normal cells. An extract from the leaves of Tetraclinis articulata (Vahl) Mast. (Cupressaceae) showed a marked cytotoxicity (IC50 = 0.37 ± 0.03 µg/mL) and selectivity (selectivity index = 378.3) against the lung cancer cells; cisplatin, 5-fluorouracil, and an extract from the leaves of Taxus baccata L. (Taxaceae) were less cytotoxic and selective. Extracts from Cascabela thevetia (L.) Lippold (Apocynaceae), Frangula alnus Mill. (Rhamnaceae), Iberis ciliata subsp. contracta (Pers.) Moreno (Brassicaceae), Juniperus macrocarpa Sm (Cupressaceae), and Pancratium maritimum L. (Amaryllidaceae) also showed selective cytotoxicity (selectivity index > 10). Active extracts were also tested against a panel of cancer cell lines from a variety tissues. The plants identified in this work are potential sources of natural compounds with selective toxicity towards cancer cells.Universidad de Sevilla VPPI-I.

Pediatric Chagas disease in the non-endemic area of Madrid: A fifteen-year review (2004-2018)

Background: Chagas disease (CD) has become an emerging global health problem in association with the immigration of individuals from endemic areas (in LatinAmerica) to other countries.Spain is the country in Europe with the highest number of CD cases. Concerning pediatric CD, treatment is not only better tolerated by younger children but also has greater cure possibilities. The aim of this study was to describe clinical and epidemiological aspects of CD in a pediatric population diagnosed of 10 hospitals in the Community of Madrid during the 2004-2018 period, as well as the safety and efficacy of CD treatment on this population. Methodology/principal findings: A multicenter, retrospective, descriptive study was conducted. The studied population included all identified children under the age of 18 with a diagnosis of CD. Diagnosis was performed with a positive parasitological test (with subsequent confirmation) or confirmed persistence of positive serology beyond 9 months, for children younger than one year-old, and with two different positive serological tests, for children older than one. Fifty-one children were included (59% male; 50.9% born in Spain). All mothers were from Latin America. The median age at diagnosis was 0.7 months for those under one year of age, and 11.08 years for those older than one year-old. Only one case presented a symptomatic course (hydrops faetalis, haemodynamic instability at birth, ascites, anaemia). For 94% treatment was completed. Considering patients who received benznidazole (47), AE were recorded in 48,9%. Among the 32 patients older than one year-old treated with benznidazole, 18 (56.25%) had adverse events whereas in the 15 under one year, 5(33,3%) did. Eigtheen (78.2%) of the patients with benznidazole AE were older than one year-old(median age 11.4 years). Of the patients treated with nifurtimox (9), AE were reported in 3 cases (33,3%). Cure was confirmed in 80% of the children under one year-old vs 4.3% in those older (p<0.001). Loss to follow- up occurred in 35.3% of patients. Conclusions/significances: Screening programs of CD since birth allow early diagnosis and treatment, with a significantly higher cure rate in children treated before one year of age, with lower incidence of adverse events. The high proportion of patients lost to follow-up in this vulnerable population is of concern.S

Importance of genetic sequencing studies in managing chronic neonatal diarrhea: a case report of a novel variant in the glucose–galactose transporter SLC5A1

IntroductionCongenital glucose–galactose malabsorption (CGGM) is a rare autosomal recessive disorder that primarily causes chronic intractable diarrhea. This study aims to describe the clinical history, laboratory profile, diagnostic workflow, and management of the first patient reported with CGGM in Mexico.MethodsThe case involves a Mexican female infant with recurrent admissions to the emergency room since birth due to chronic diarrhea.ResultsThe infant was born at term by C-section with a birth weight of 3.120 kg and height of 48 cm for consanguineous parents. She had been breastfed until day 5 of her life when she presented lethargy, diarrhea, abdominal discomfort, and jaundice. During the first evaluation at the emergency room, the significant laboratory finding was blood tyrosine elevation; afterward, amino acid and succinylacetone determinations were obtained, discarding tyrosinemia. When admitted to the hospital, an abdominal ultrasound detected a duplex collecting system. At this time, rice formula was introduced to the patient. She was discharged with jaundice improvement, but diarrhea persisted. Several formula changes had been made from rice to extensively hydrolyzed casein protein to whey-based, with no clinical improvement; the patient still had 10–12 excretions daily. In the second hospitalization, the patient presented anemia, severe dehydration, hyperammonemia, and renal tubular acidosis. A next-generation sequencing panel for inborn errors of metabolism and congenital diarrhea was performed, identifying a homozygous variant in SLC5A1 (c.1667T &gt; C). The diagnosis of CGGM was made at 3 months of age. The infant was initially treated with a modular galactose–glucose-free formula with oil, fructose, casein, minerals, and vitamins until a commercial fructose-based formula was introduced. This led to a complete resolution of diarrhea and improved nutritional status.DiscussionDiagnosing CGGM is challenging for clinicians, and next-generation sequencing is a valuable tool for providing appropriate treatment. More detailed information on patients with this condition might lead to possible phenotype–genotype correlations. This case's primary clinical and biochemical findings were chronic diarrhea, anemia, jaundice, renal tubular acidosis, hyperammonemia, and initial hypertyrosinemia. Symptoms were resolved entirely with the fructose-based formula

Efectividad de un protocolo de entrenamiento con el dispositivo de facilitación de movimiento cervical en sujetos con déficit de fuerza de la musculatura profunda cervical. Estudio piloto

Neck pain is one of the major public health problems, which has a great impact on the quality of people's lives, with a high prevalence and recurrence rate. The deep cervical muscles play a key role in neck stability. Deficits in deep cervical muscle strength are related to different clinical conditions: cervicogenic dizziness, cervical radiculopathy, chronic mechanical neck pain, cervical pain, and cervical instability. Training protocols can help to improve pain, cervical function, posture, and cross-sectional area. However, there are no training protocols in subjects with strength deficit in deep cervical muscles, including deep neck extensor and flexor muscles. The cervical device treatment (CDAT) allows us to train the cervical flexor and extensor muscle in a simple and comfortable way. The purpose of this study is to evaluate the clinical results in upper cervical range of motion, endurance, and self-perceived functional capacity by a training protocol with the new device for cervical treatment (GD) and the conventional training protocol (GH) versus a control group (GC) in subjects with cervical deep muscle strength deficit

Prácticas artísticas para la sensibilización de la comunidad universitaria hacia las persona afectadas de alzheimer y otras demencias

Depto. de Escultura y Formación ArtísticaFac. de Bellas ArtesFALSEsubmitte

Dual latent tuberculosis screening with tuberculin skin tests and QuantiFERON-TB assays before TNF-α inhibitor initiation in children in Spain

Tumor-necrosis-factor-α inhibitors (anti-TNF-α) are associated with an increased risk of tuberculosis (TB) disease, primarily due to reactivation of latent TB infection (LTBI). We assessed the performance of parallel LTBI screening with tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube assays (QFT-GIT) before anti-TNF-α treatment in children with immune-mediated inflammatory disorders in a low TB-burden setting. We conducted a multicenter cohort study involving 17 pediatric tertiary centers in Spain. LTBI was defined as the presence of a positive TST and/or QFT-GIT result without clinical or radiological signs of TB disease. A total of 270 patients (median age:11.0 years) were included, mainly with rheumatological (55.9%) or inflammatory bowel disease (34.8%). Twelve patients (4.4%) were diagnosed with TB infection at screening (LTBI, n = 11; TB disease, n = 1). Concordance between TST and QFT-GIT results was moderate (TST+/QFT-GIT+, n = 4; TST-/QFT-GIT+, n = 3; TST+/QFT-GIT-, n = 5; kappa coefficient: 0.48, 95% CI: 0.36-0.60). Indeterminate QFT-GIT results occurred in 10 patients (3.7%) and were associated with young age and elevated C-reactive protein concentrations. Eleven of 12 patients with TB infection uneventfully completed standard LTBI or TB treatment. During a median follow-up period of 6.4 years, only 2 patients developed TB disease (incidence density: 130 (95% CI: 20-440) per 100,000 person-years), both probable de novo infections. Conclusion: A substantial number of patients were diagnosed with LTBI during screening. The dual strategy identified more cases than either of the tests alone, and test agreement was only moderate. Our data show that in children in a low TB prevalence setting, a dual screening strategy with TST and IGRA before anti-TNF-α treatment is effective