Polysialylated neuropilin-2 enhances human dendritic cell migration through the basic C-terminal region of CCL21.

Free Access at: http://glycob.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=20488940Dendritic cell (DC) migration to secondary lymphoid organs is a critical step to properly exert its role in immunity; and predominantly depends on the interaction of the chemokine receptor CCR7 with its ligands CCL21 and CCL19. Polysialic acid (PSA) has been recently reported to control CCL21-directed migration of mature DCs. Here; we first demonstrate that PSA present on human mature monocyte-derived dendritic cells did not enhance chemotactic responses to CCL19. We have also explored the molecular mechanisms underlying the selective enhancing effect of PSA on CCL21-driven chemotaxis of DCs. In this regard; we found out that prevention of DC polysialylation decreased CCL21 activation of JNK and Akt signaling pathways; both associated with CCR7-mediated chemotaxis. We also report that the enhanced PSA-mediated effect on DC migration towards CCL21 relied on the highly basic C-terminal region of this chemokine; and depended on the PSA acceptor molecule neuropilin-2 (NRP2) and on the polysialyltransferase ST8SiaIV. Altogether; our data indicate that the CCR7/CCL21/NRP2/ST8SiaIV functional axis constitutes an important guidance clue for DC targeting to lymphoid organs.This work was supported by research grant from Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo (FISPI0708879 to MAV).Peer reviewe

Thermodynamic Parameters of Adsorption from Systems Activated Carbon Chlordiazepoxide and Activated Carbon-Diazepam Parámetros termodinámicos de adsorción de los sistemas carbón activado-clordiazepóxido y carbón activado-diazepam

Resumen Se estudian los parámetros termodinámicos de la adsorción de clordiazepóxido y diazepam en seis carbonos activados: Norit B, BDH, Merck, Panreac, M1 y M, en fluido gástrico simulado. Los materiales se caracterizan por: FTIR, pHzpc y adsorción de N 2 a 77 K. La porosidad fue interpretada por las ecuaciones de Dubinin-Radushkevich y BET. Los resultados muestran la relación entre el aumento de la temperatura, las características de cada adsorbente y el comportamiento de estos fármacos. Los valores positivos de todas las entalpías isostéricas de adsorción determinadas a partir de la pendiente de Van 't Hoff (R 2 > 97), indican la naturaleza endotérmica del proceso de adsorción, así como la ∆G < 0 con el incremento de la temperatura. La ∆G < 0 en todos los casos explica el carácter espontáneo del proceso de adsorción. Los valores positivos ∆S dejan claramente que la aleatoriedad se incrementó en la interfaz sólido-solución durante el proceso de adsorción. Palabras clave: carbón activado, adsorción, parámetros termodinámicos. Abstract It is study the thermodynamic parameters of chlordiazepoxide and diazepam drugs adsorbed onto six activated carbons: Norit B, BDH, Merck, Panreac, M1 and M, from simulated gastric fluid at pH 1,2 for 4 h were characterized by FTIR, pH zpc, and adsorption of N 2 to 77 K. The results of porosity were interpreted with the Dubinin-Radushkevich's models and BET' equation. By UV visible spectra residual drugs were monitored. The results show relationship between: increased of temperature, the characteristics of each adsorbent and the behavior of these drugs in acid solution. The positive values of all the isosteric adsorption enthalpies determined from the slope Van't Hoff plot (R 2 > 97), indicate the nature endothermic process of adsorption. The ∆G<0 in all cases explained the spontaneous character of the adsorption process and the positive values of ∆S state clearly that the randomness increased at the solidsolution interface during adsorption process

Patient preferences and treatment safety for uncomplicated vulvovaginal candidiasis in primary health care

<p>Abstract</p> <p>Background</p> <p>Vaginitis is a common complaint in primary care. In uncomplicated candidal vaginitis, there are no differences in effectiveness between oral or vaginal treatment. Some studies describe that the preferred treatment is the oral one, but a Cochrane's review points out inconsistencies associated with the report of the preferred way that limit the use of such data. Risk factors associated with recurrent vulvovaginal candidiasis still remain controversial.</p> <p>Methods/Design</p> <p>This work describes a protocol of a multicentric prospective observational study with one year follow up, to describe the women's reasons and preferences to choose the way of administration (oral vs topical) in the treatment of not complicated candidal vaginitis. The number of women required is 765, they are chosen by consecutive sampling. All of whom are aged 16 and over with vaginal discharge and/or vaginal pruritus, diagnosed with not complicated vulvovaginitis in Primary Care in Madrid.</p> <p>The main outcome variable is the preferences of the patients in treatment choice; secondary outcome variables are time to symptoms relief and adverse reactions and the frequency of recurrent vulvovaginitis and the risk factors. In the statistical analysis, for the main objective will be descriptive for each of the variables, bivariant analysis and multivariate analysis (logistic regression).. The dependent variable being the type of treatment chosen (oral or topical) and the independent, the variables that after bivariant analysis, have been associated to the treatment preference.</p> <p>Discussion</p> <p>Clinical decisions, recommendations, and practice guidelines must not only attend to the best available evidence, but also to the values and preferences of the informed patient.</p

Land- and water-based exercise intervention in women with fibromyalgia: the al-andalus physical activity randomised controlled trial

Background The al-Andalus physical activity intervention study is a randomised control trial to investigate the effectiveness of a land- and water-based exercise intervention for reducing the overall impact of fibromyalgia (primary outcome), and for improving tenderness and pain-related measures, body composition, functional capacity, physical activity and sedentary behaviour, fatigue, sleep quality, health-related quality of life, and cognitive function (secondary outcomes) in women with fibromyalgia. Methods/Design One hundred eighty women with fibromyalgia (age range: 35-65 years) will be recruited from local associations of fibromyalgia patients in Andalucía (Southern Spain). Patients will be randomly assigned to a usual care (control) group (n = 60), a water-based exercise intervention group (n = 60) or a land-based exercise intervention group (n = 60). Participants in the usual care group will receive general physical activity guidelines and participants allocated in the intervention groups will attend three non-consecutive training sessions (60 min each) per week during 24 weeks. Both exercise interventions will consist of aerobic, muscular strength and flexibility exercises. We will also study the effect of a detraining period (i.e., 12 weeks with no exercise intervention) on the studied variables. Discussion Our study attempts to reduce the impact of fibromyalgia and improve patients' health status by implementing two types of exercise interventions. Results from this study will help to assess the efficacy of exercise interventions for the treatment of fibromyalgia. If the interventions would be effective, this study will provide low-cost and feasible alternatives for health professionals in the management of fibromyalgia. Results from the al-Andalus physical activity intervention will help to better understand the potential of regular physical activity for improving the well-being of women with fibromyalgia.This study was supported by the Consejeria de Turismo, Comercio y Deporte (CTCD-201000019242-TRA), the Spanish Ministry of Science and Innovation (I + D + I DEP2010-15639, grants: BES-2009-013442, BES-2011-047133, RYC-2010-05957, RYC-2011-09011), the Swedish Heart-Lung Foundation (20090635), the Spanish Ministry of Education (AP-2009-3173), Granada Research of Excelence Initiative on Biohealth (GREIB), Campus BioTic, University of Granada, Spain and European University of Madrid. Escuela de Estudios Universitarios Real Madrid. 2010/04RM

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Polysialic acid is required for neuropilin-2a/b-mediated control of CCL21-driven chemotaxis of mature dendritic cells and for their migration in vivo

8 p.-3 fig.Migration of mature dendritic cells (mDCs) to secondary lymphoid organs is required for the development of immunity.Recently, we reported that polysialic acid (PSA) and the transmembrane glycoprotein neuropilin-2 (NRP2) control mDC chemotaxis to CCL21 and that this process is dependent on the C-terminal basic region of the chemokine. Herein, we provide further insight into the molecular components controlling PSA regulated chemotaxis in mDCs. In the present study, we demonstrate that human mDCs express the NRP2 isoforms NRP2a and NRP2b,that both of them are susceptible to polysialylation and that polysialylation is required to specifically enhance chemotaxis toward CCL21 in mDCs. The results presented suggest that PSA attached to NRP2 isoforms acts as a binding module for the CCL21 chemokine, thereby facilitating its presentation to the chemokine receptor CCR7. To investigate the relevance of polysialylation on mDC migration, a xenograft mouse model was used and the migration of human DCs to mouse lymph nodes analyzed. Here, we demonstrate that the depletion of PSA from mDCs results in a drastic reduction in the migration of the cells to draining popliteal lymph nodes. With this finding, we provide first evidence that PSA is a crucial factor for in vivo migration of mDCs to lymph nodes.This work was supported by research grant from Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo (FIS-PI0708879 to M.A.V.), and from Genoma España (MEICA project).Peer reviewe

SEOM clinical guidelines for the treatment of advanced prostate cancer (2020)

The treatment of advanced prostate cancer has evolved due to recent advances in molecular research and new drug development. Dynamic aberrations in the androgen receptor, DNA repair genes, PTEN-PI3K, and other pathways drive the behavior of advanced prostate cancer allowing a better selection of therapies in each patient. Tumor testing for BRCA1 and BRCA2 is recommended for patients with metastatic prostate cancer, also considering a broad panel to guide decisions and genetic counseling. In symptomatic metastatic patients, castration should be stared to palliate symptoms and prolong survival. In high-risk or high-volume metastatic hormone-naïve patients, castration should be combined with docetaxel, abiraterone, enzalutamide or apalutamide. Radiotherapy to the primary tumor combined with systemic therapy is recommended in low-volume mHNPC patients. In patients with non-metastatic castration-resistant tumors, risk stratification can define the frequency of imaging. Adding enzalutamide, darolutamide or apalutamide to these patients prolongs metastasis-free and overall survival, but potential adverse events need to be taken into consideration. The choice of docetaxel, abiraterone or enzalutamide for treating metastatic castration-resistant patients depends on previous therapies, with cabazitaxel being also recommended after docetaxel. Olaparib is recommended in BRCA1/BRCA2 mutated castration-resistant patients after progression on at least one new hormonal therapy. Aggressive variants of prostate cancer respond to platinum-based chemotherapy. To optimize treatment efficiency, oncologists should incorporate all of these advances into an overall therapeutic strategy