Effect of fluvastatin therapy of the pattern of protein expression in monocytes of patients in primary antiphospholipid syndrome

Comunicaciones a congreso

Inhibition of heme oxygenase-1 interferes with the transforming activity of the Kaposi sarcoma herpesvirus-encoded G protein-coupled receptor

Heme oxygenase-1 (HO-1), the inducible enzyme responsible for the rate-limiting step in the heme catabolism, is expressed in AIDS-Kaposi sarcoma (KS) lesions. Its expression is up-regulated by the Kaposi sarcoma-associated herpesvirus (KSHV) in endothelial cells, but the mechanisms underlying KSHV-induced HO-1 expression are still unknown. In this study we investigated whether the oncogenic G protein-coupled receptor (KSHV-GPCR or vGPCR), one of the key KSHV genes involved in KS development, activated HO-1 expression. Here we show that vGPCR induces HO-1 mRNA and protein levels in fibroblasts and endothelial cells. Moreover, targeted knock-down gene expression of HO-1 by small hairpin RNA and chemical inhibition of HO-1 enzymatic activity by tin protoporphyrin IX (SnPP), impaired vGPCR-induced survival, proliferation, transformation, and vascular endothelial growth factor (VEGF)-A expression. vGPCR-expressing cells implanted in the dorsal flank of nude mice developed tumors with elevated HO-1 expression and activity. Chronic administration of SnPP to the implanted mice, under conditions that effectively blocked HO-1 activity and VEGF-A expression in the transplanted cells, strikingly reduced tumor growth, without apparent side effects. On the contrary, administration of the HO-1 inducer cobalt protoporphyrin (CoPP) further enhanced vGPCR-induced tumor growth. These data postulate HO-1 as an important mediator of vGPCR-induced tumor growth and suggest that inhibition of intratumoral HO-1 activity by SnPP may be a potential therapeutic strategy. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.Fil:Tanos, T. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Coso, O.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina

Diagnostic value of quantitative SPECT/CT in assessing active sacroiliitis in patients with axial spondylarthritis and/or inflammatory low back pain

Background. The diagnostic accuracy of bone scintigraphy (BS) increases with SPECT/CT imaging. It would therefore be appropriate to reassess the diagnostic utility of scintigraphy in sacroiliitis with axial spondyloarthritis (SpA). The aim of this study was to compare the diagnostic performance of MRI, SPECT/CT and a combination of both techniques in sacroiliitis, and to evaluate the correlation between quantitative SPECT/CT indices and quantitative MRI inflammatory lesion scores. Methods. Thirty-one patients with active SpA and 22 patients with inflammatory low back pain underwent MRI and SPECT/CT of the sacroiliac joints. The diagnostic accuracy of both techniques was calculated using clinical diagnosis as the gold standard. The correlation between MRI and SPECT/CT was calculated by comparing the SPECT/CT activity indices and the Berlin/SPARCC scoring systems for MRI. Results. The sensitivity and specificity values in quantitative SPECT/CT, taking the sacroiliac/promontory ratio of >1.36 as the cut-off value, were close to those from MRI published in the literature. The combination of both techniques increased sensitivity while maintaining high specificity. There was a moderate correlation between SPECT/CT and MRI total scores. This correlation was improved by using solely the MRI inflammation scores. Conclusion. Quantitative SPECT/CT showed better diagnostic accuracy than planar scintigraphy and showed a moderate correlation with MRI scores in active sacroiliitis. The combination of both tests increased the diagnostic accuracy. Quantitative SPECT/CT could play a relevant role in the diagnosis of active sacroiliitis in patients with high a suspicion of SpA and a negative/inconclusive MRI test or in patients with whom MRI studies cannot be carried out.Fundamento. La precisión diagnóstica de la gammagrafía ósea (GO) aumenta con las imágenes SPECT/TAC haciendo conveniente reevaluar su utilidad diagnóstica en la sacroilitis de la espondiloartritis axial (EA). El objetivo fue comparar el rendimiento diagnóstico de la resonancia magnética (RM), la SPECT/TC y ambas pruebas combinadas, y evaluar la correlación entre los índices cuantitativos de ambas técnicas. Métodos. A 31 pacientes con EA activa y 22 con lumbalgia inflamatoria se les realizó una RM y una SPECT/TC de las articulaciones sacroilíacas y se calculó la precisión diagnóstica de ambas técnicas respecto al diagnóstico clínico. La correlación entre ambas pruebas se calculó comparando los índices de actividad del SPECT/TC con los sistemas de puntuación Berlín y SPARCC de RM. Resultados. Los valores de sensibilidad y especificidad de la SPECT/TC cuantitativa, tomando como punto de corte el cociente sacroilíaca/promontorio >1,36, fueron similares a los publicados para la RM. La combinación de ambas técnicas aumentó la sensibilidad manteniendo una alta especificidad. La correlación entre las escalas totales de RM y SPECT/TC fue moderada y mejoraba al utilizar únicamente las escalas de inflamación. Conclusiones. La SPECT/TC cuantitativa muestra una mejor precisión diagnóstica que la GO planar en la sacroilitis activa y una correlación moderada con las puntuaciones de RM. La combinación de ambas técnicas aumenta la precisión diagnóstica. Por tanto, la SPECT/TAC cuantitativa podría tener un papel relevante en el diagnóstico de sacroilitis en pacientes con alta sospecha de EA y RM negativa/no concluyente o en aquellos pacientes en los que no se pueda realizar una RM

Recessive dystrophic epidermolysis bullosa: the origin of the c.6527insC mutation in the Spanish population

This work was supported by grants from the Spanish Ministry of Science and Innovation (MICINN) (SAF2007-61019 and SAF 2010-16976), INTRA ⁄08 ⁄714.1 and INTRA ⁄09 ⁄758 from the Biomedical Network Research Centre on Rare Diseases (CIBERER) and S2010 ⁄BMD-2420 (CELLCAM) from Comunidad de Madrid

Usual dietary intake, nutritional adequacy and food sources of calcium, phosphorus, magnesium and vitamin D of spanish children aged one to dagger

Bone problems in the population begin to be establish in childhood. The present study aims to assess the usual calcium, phosphorus, magnesium, and vitamin D intakes, along with the food sources of these nutrients, in Spanish children participating in the EsNuPI (Estudio Nutricional en Población Infantil Española) study. Two 24 h dietary recalls were applied to 1448 children (1 to <10 years) divided into two sub-samples: one reference sample (RS) of the general population [n = 707] and another sample which exclusively included children consuming enriched or fortified milks, here called “adapted milks” (AMS) [n = 741]. Estimation of the usual intake shows that nutrient intake increased with age for all nutrients except vitamin D. Using as reference the Dietary Reference Values from the European Food Safety Authority (EFSA), calcium and magnesium intakes were found to be below the average requirement (AR) and adequate intake (AI), respectively, in a considerable percentage of children. Furthermore, phosphorus exceeded the AI in 100% of individuals and vitamin D was lower than the AI in almost all children studied. The results were very similar when considering only plausible reporters. When analyzing the food sources of the nutrients studied, milk and dairy products contributed the most to calcium, phosphorus, magnesium, and vitamin D. Other sources of calcium were cereals and vegetables; for phosphorus: meat, meat products, and cereals; for magnesium: cereals and fruits; and, for vitamin D: fish and eggs. These results highlight the desirability of improving the intake concerning these nutrients, which are involved in bone and metabolic health in children. The AMS group appeared to contribute better to the adequacy of those nutrients than the RS group, but both still need further improvement. Of special interest are the results of vitamin D intakes, which were significantly higher in the AMS group (although still below the AI), independent of age

Evaluation of different bowel preparations for small bowel capsule endoscopy: a prospective, randomized, controlled study

To obtain an adequate view of the whole small intestine during capsule endoscopy (CE) a clear liquid diet and overnight fasting is recommended. However, intestinal content can hamper vision in spite of these measures. Our aim was to evaluate tolerance and degree of intestinal cleanliness during CE following three types of bowel preparation. PATIENTS AND METHODS: This was a prospective, multicenter, randomized, controlled study. Two-hundred ninety-one patients underwent one of the following preparations: 4 L of clear liquids (CL) (group A; 92 patients); 90 mL of aqueous sodium phosphate (group B; 89 patients); or 4 L of a polyethylene glycol electrolyte solution (group C; 92 patients). The degree of cleanliness of the small bowel was classified by blinded examiners according to four categories (excellent, good, fair or poor). The degree of patient satisfaction, gastric and small bowel transit times, and diagnostic yield were measured. RESULTS: The degree of cleanliness did not differ significantly between the groups (P = 0.496). Interobserver concordance was fair (k = 0.38). No significant differences were detected between the diagnostic yields of the CE (P = 0.601). Gastric transit time was 35.7 +/- 3.7 min (group A), 46.1 +/- 8.6 min (group B) and 34.6 +/- 5.0 min (group C) (P = 0.417). Small-intestinal transit time was 276.9 +/- 10.7 min (group A), 249.7 +/- 13.1 min (group B) and 245.6 +/- 11.6 min (group C) (P = 0.120). CL was the best tolerated preparation. Compliance with the bowel preparation regimen was lowest in group C (P = 0.008). CONCLUSIONS: A clear liquid diet and overnight fasting is sufficient to achieve an adequate level of cleanliness and is better tolerated by patients than other forms of preparation

YES1 drives lung cancer growth and progression and predicts sensitivity to dasatinib

Rationale: The characterization of new genetic alterations is essential to assign effective personalized therapies in non–small cell lung cancer (NSCLC). Furthermore, finding stratification biomarkers is essential for successful personalized therapies. Molecular alterations of YES1, a member of the SRC (proto-oncogene tyrosine-protein kinase Src) family kinases (SFKs), can be found in a significant subset of patients with lung cancer. Objectives: To evaluate YES1 (v-YES-1 Yamaguchi sarcoma viral oncogene homolog 1) genetic alteration as a therapeutic target and predictive biomarker of response to dasatinib in NSCLC. Methods: Functional significance was evaluated by in vivo models of NSCLC and metastasis and patient-derived xenografts. The efficacy of pharmacological and genetic (CRISPR [clustered regularly interspaced short palindromic repeats]/Cas9 [CRISPR-associated protein 9]) YES1 abrogation was also evaluated. In vitro functional assays for signaling, survival, and invasion were also performed. The association between YES1 alterations and prognosis was evaluated in clinical samples. Measurements and Main Results: We demonstrated that YES1 is essential for NSCLC carcinogenesis. Furthermore, YES1 overexpression induced metastatic spread in preclinical in vivo models. YES1 genetic depletion by CRISPR/Cas9 technology significantly reduced tumor growth and metastasis. YES1 effects were mainly driven by mTOR (mammalian target of rapamycin) signaling. Interestingly, cell lines and patient-derived xenograft models with YES1 gene amplifications presented a high sensitivity to dasatinib, an SFK inhibitor, pointing out YES1 status as a stratification biomarker for dasatinib response. Moreover, high YES1 protein expression was an independent predictor for poor prognosis in patients with lung cancer. Conclusions: YES1 is a promising therapeutic target in lung cancer. Our results provide support for the clinical evaluation of dasatinib treatment in a selected subset of patients using YES1 status as predictive biomarker for therapy

Key Factors Associated With Pulmonary Sequelae in the Follow-Up of Critically Ill COVID-19 Patients

Introduction: Critical COVID-19 survivors have a high risk of respiratory sequelae. Therefore, we aimed to identify key factors associated with altered lung function and CT scan abnormalities at a follow-up visit in a cohort of critical COVID-19 survivors. Methods: Multicenter ambispective observational study in 52 Spanish intensive care units. Up to 1327 PCR-confirmed critical COVID-19 patients had sociodemographic, anthropometric, comorbidity and lifestyle characteristics collected at hospital admission; clinical and biological parameters throughout hospital stay; and, lung function and CT scan at a follow-up visit. Results: The median [p25–p75] time from discharge to follow-up was 3.57 [2.77–4.92] months. Median age was 60 [53–67] years, 27.8% women. The mean (SD) percentage of predicted diffusing lung capacity for carbon monoxide (DLCO) at follow-up was 72.02 (18.33)% predicted, with 66% of patients having DLCO < 80% and 24% having DLCO < 60%. CT scan showed persistent pulmonary infiltrates, fibrotic lesions, and emphysema in 33%, 25% and 6% of patients, respectively. Key variables associated with DLCO < 60% were chronic lung disease (CLD) (OR: 1.86 (1.18–2.92)), duration of invasive mechanical ventilation (IMV) (OR: 1.56 (1.37–1.77)), age (OR [per-1-SD] (95%CI): 1.39 (1.18–1.63)), urea (OR: 1.16 (0.97–1.39)) and estimated glomerular filtration rate at ICU admission (OR: 0.88 (0.73–1.06)). Bacterial pneumonia (1.62 (1.11–2.35)) and duration of ventilation (NIMV (1.23 (1.06–1.42), IMV (1.21 (1.01–1.45)) and prone positioning (1.17 (0.98–1.39)) were associated with fibrotic lesions. Conclusion: Age and CLD, reflecting patients’ baseline vulnerability, and markers of COVID-19 severity, such as duration of IMV and renal failure, were key factors associated with impaired DLCO and CT abnormalities