Eficacia de leflunomida 100 mg semanales comparado con dosis bajas de metotrexate en pacientes con artritis reumatoide activa. Estudio clínico doble ciego aleatorizado

ObjectiveTo determine the clinical efficacy and safety of Leflunomide (LFN) 100 mg/week compared to low dose Methotrexate (MTX) 10 mg/week in a double-blind, randomized, controlled trial with 52 weeks of follow up in Rheumatoid Arthritis (RA) patients.Patients and methodsPatients who met ARC1987 criteria for RA were included. All patients had medical records, including laboratory tests and hand X-rays. Clinical evaluations for improvement and ACR and EULAR response criteria were performed. Statistical analysis for independent's samples between both groups defined a P value of ≤ .05. Safety was evaluated by comparing the proportion of adverse events (AE) registered.ResultsOf 90 patients screened; five were withdrawn; the remaining 85 patients were randomised: 43 LFN and 42 MTX. Sixty-three patients completed the study; 72% in the LFN group and 74.4% in the MTX group. ACR20 improvement criteria were achieved by LFN group in 90.3%, and in MTX 78.1% (P = .14) at week 52. EULAR improvement criteria applied at the end point showed a DAS28 score for the LFN group of 3.45, and for the MTX group was 3.67(P = .43). Total withdrawals, including loss during follow up, AE and lack of efficacy for each group was 12 patients in the LFN group, and 10 patients in the MTX group. Regarding safety, no serious AE of a life threatening nature were reported.ConclusionsThese outcomes confirm that LFN 100 mg/week offers an adequate and sustained improvement effect on the clinical manifestations of RA, similar to low dose treatment with MTX 10 mg/every week after 52 weeks of follow up; it may be a good therapeutic option alone or in combination with others anti-rheumatic drugs.     

History of myocardial iron loading is a strong risk factor for diabetes mellitus and hypogonadism in adults with β thalassemia major

Endocrinopathies are common complications of transfusional hemosiderosis among patients with β thalassemia major (TM). Previous studies had shown associations between some endocrinopathies and iron overload of the myocardium, liver and/or endocrine organs as assessed by MRI techniques. This retrospective analysis of 92 patients with TM (median age 36 yr) from a tertiary adult thalassemia unit in UK aimed to determine independent risk factors associated with endocrinopathies among these patients. Unlike previous studies, longitudinal data on routine measurements of iron load [worst myocardial and liver T2* values since 1999, worst LIC by MRI‐R2 since 2008 and average 10‐yr serum ferritin (SF)] up to April 2010 together with demographic features and age of initiating chelation were analyzed for associations with endocrinopathies. The most common endocrinopathies in this cohort were hypogonadism (67%) and diabetes mellitus (DM) (41%), and these were independently associated with myocardial T2* <20 ms (P < 0.001 and P = 0.008, respectively) and increased age (P = 0.002 and P = 0.016, respectively). DM and hypogonadism were independently associated with average SF >1250 μg/L (P = 0.003) and >2000 μg/L (P = 0.047), respectively. DM was also associated with initial detection of abnormal myocardial T2* at an older age (30 yr vs. 24 yr, P = 0.039). An abnormal myocardial T2* may therefore portend the development of DM and hypogonadism in patients with TM.     

Lymphokine-induced phagocytosis in angiocentric immunoproliferative lesions (AIL) and malignant lymphoma arising in AIL

A factor that augmented the phagocytosis of IgG-coated ox red blood cells by the human monocyte/macrophage line U937 was identified in cell culture supernatants from two of two patients with angiocentric peripheral T cell lymphomas, three of three patients with angiocentric immunoproliferative lesions that were not frankly malignant, and one of two patients with T lymphoblastic malignancies. The factor was not present in supernatants derived from 14 nonangiocentric peripheral T cell lymphomas of other histologic types nor in ten cases of B cell lymphoma and two cases of Hodgkin's disease. A similar factor was present in the supernatants of concanavalin A (Con A)-stimulated normal peripheral blood mononuclear cells and in the supernatants of IL-2- dependent T cell lines derived from normal peripheral blood. The factor had an apparent mol wt of greater than 50,000 daltons, was heat labile (100 degrees C for two minutes), and stable at pH 2.0. Its stimulation of phagocytosis was independent of any increase in number of Fc receptors. Thus, this factor is probably not gamma-interferon. This factor may play a pathogenetic role in the hemophagocytic syndromes associated with certain T cell malignancies and immunodeficient states.     

乳腺浸润性微乳头状癌(IMPC) 29例临床分析

 目的  研究乳腺浸润性微乳头状癌(invasive micropapillary carcinoma of the breast,IMPC)的临床病理特征以及生存预后分析。方法  选择2006年6月至2013年6月在本院收治的IMPC 29例,中位随访42个月,分析其临床病理特点、局部复发率、远处转移率及总生存率(overall survival,OS)等生存预后指标;与320例浸润性导管癌(invasive ductal carcinoma,IDC)病例进行对照,分析比较两组间的临床病理特点及生存预后指标。为进一步探讨IMPC病理类型对于生存预后的影响,将58例IDC与29例IMPC进行2∶1配对对照研究,分析比较两组间的生存预后指标。结果   29例IMPC中23例(79.3%)发生淋巴结转移,其中4枚及以上淋巴结转移的有15例(51.7%),18例(62.1%)伴有脉管侵犯。分子分型以Luminal B型为主(21例)。3年无局部复发生存率(local recurrence free survival,LRFS)、无转移生存率(metastasis free survival,MFS)、OS分别为:74%、86%、90%。Cox回归分析得出淋巴结转移个数是IMPC局部复发的影响因素(P=0.048)。与IDC组比较,IMPC组肿瘤体积大(3.70 cm vs.2.81 cm,P=0.007),淋巴结转移率高(79.3% vs.45.0%,P<0.001),淋巴结转移个数多(5.90 vs.2.16,P=0.003),淋巴结分级高分级比例较高(N2:24.1% vs.7.5%,N3:27.6% vs.6.9%,P<0.001),脉管侵犯率高(62.1% vs.20.0%,P<0.001),手术方式中标准根治术比例高(24.2% vs.3.1%,P<0.001),化疗方式中新辅助化疗比例高(31.0% vs.9.1%,P<0.001),其余方面差异无统计学意义。Log Rank检验生存分析得出IMPC组的LRFS显著低于IDC组(P=0.001),但两组间的MFS及OS差异无统计学意义(P=0.074及0.106)。将58例IDC与29例IMPC进行配对对照研究,Log Rank检验生存分析得出两组间的LFRS、MFS与OS差异均无统计学意义(P=0.586、0.965、0.920)。 结论   乳腺IMPC是一类预后较差的特殊类型乳腺癌,其较高的淋巴脉管侵犯性而非这一病理类型,与肿瘤的生存预后相关。     

Deciphering principles of morphogenesis from temporal and spatial patterns on the integument

Background : How tissue patterns form in development and regeneration is a fundamental issue remaining to be fully understood. The integument often forms repetitive units in space (periodic patterning) and time (cyclic renewal), such as feathers and hairs. Integument patterns are visible and experimentally manipulatable, helping us reveal pattern formative processes. Variability is seen in regional phenotypic specificities and temporal cycling at different physiological stages. Results: Here we show some cellular/molecular bases revealed by analyzing integument patterns. (1) Localized cellular activity (proliferation, rearrangement, apoptosis, differentiation) transforms prototypic organ primordia into specific shapes. Combinatorial positioning of different localized activity zones generates diverse and complex organ forms. (2) Competitive equilibrium between activators and inhibitors regulates stem cells through cyclic quiescence and activation. Conclusions: Dynamic interactions between stem cells and their adjacent niche regulate regenerative behavior, modulated by multi‐layers of macro‐environmental factors (dermis, body hormone status, and external environment). Genomics studies may reveal how positional information of localized cellular activity is stored. In vivo skin imaging and lineage tracing unveils new insights into stem cell plasticity. Principles of self‐assembly obtained from the integumentary organ model can be applied to help restore damaged patterns during regenerative wound healing and for tissue engineering to rebuild tissues. Developmental Dynamics 244:905–920, 2015. © 2015 Wiley Periodicals, Inc.     

l-Menthol alleviates cigarette smoke extract induced lung injury in rats by inhibiting oxidative stress and inflammation via nuclear factor kappa B,p38 MAPK and Nrf2 signalling pathways

l-Menthol is the main ingredient of peppermint which affects various pharmacological effects such as anti-inflammation and anti-oxidative activity. In this study, we aimed to evaluate the potential effects of l-menthol on cigarette smoke extract (CSE) induced lung injury in rats. Morphology assessment results revealed that administration with l-menthol (5, 10 or 20 mg kg⁻¹ d⁻¹) significantly alleviated CSE-induced lung injury. Besides, l-menthol significantly reduced the inflammatory response by suppressing the production of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) via downregulating nuclear factor kappa B (NF-κB) and p38 MAPK pathways. Meanwhile, l-menthol decreased the levels of oxidative stress markers including malondialdehyde (MDA) and myeloperoxidase (MPO) whereas it increased the amount of glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) through activation of the Nrf2 pathway. Furthermore, the expression of MMP-9 and TIMP-1 in lungs was reduced after treatment with l-menthol, and this indicated that l-menthol might have a potential effect on airway remodeling. Moreover, immunohistochemistry analyses indicated that l-menthol could suppress the infiltration of CD4⁺ and CD8⁺ T cells in lung tissues and this was probably due to the immune regulation activity of l-menthol. Taken together, our findings support that l-menthol might be a potential candidate for the treatment of CSE-induced lung injury in rats.

l-Menthol is the main ingredient of peppermint which affects various pharmacological effects such as anti-inflammation and anti-oxidative activity.     

Large-scale preparation of size-controlled Fe3O4@SiO2 particles for electrophoretic display with non-iridescent structural colors

Monodisperse colloidal particles have promising applications in electrophoretic displays with vivid colors, reversibility and low switching times. In this study, a facile, effective and large-scale strategy for preparing size-controlled Fe₃O₄@SiO₂ particles is reported. Multiple Fe₃O₄ particles were synthesized by a modified solvothermal method using sodium citrate as a surface modifier with a binary solvent, and were then coated with a SiO₂ layer to obtain a highly negatively charged surface via a modified Stöber method. Owing to the easily controlled sizes and sufficient surface charges, Fe₃O₄@SiO₂ particles can be assembled into colloidal amorphous arrays with the balance of electrostatic repulsion and electrophoretic forces. The reflections cover wavelengths ranging from 802 to 453 nm, and were optimized by investigating the dependence of the particles on variables such as particle size, particle volume fraction, and electric field intensity. The large-scale preparation of electrically responsive Fe₃O₄@SiO₂ particles facilitates an electrophoretic display with broad-range colors, showing the practical potential in industrial application.

Fe₃O₄@SiO₂ particles were prepared on the gram-scale by selecting Na₃Cit as the modifier with binary solvent and were assembled into colloidal amorphous arrays with unique and attractive optical properties for EPD.