HDL functionality in type 1 diabetes

Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by absence of insulin secretion due to destruction of the pancreatic beta-cells. Patients with T1D exhibit an increased risk for cardiovascular disease (CVD) compared with non-diabetic subjects. It has been established that low concentration of high-density lipoprotein cholesterol (HDL-C), an independent risk marker of CVD, coincides with a reduced protective capacity against oxidative stress. However, conflicting results have been reported on the prevalence of low HDL-C levels in T1D. Interestingly, changes in composition and function of HDL particles (abnormal ratio of cholesteryl ester-to-triglyceride, reduction in the phospholipid content, reduced capacity to promote cholesterol efflux from macrophages, impaired anti-inflammatory and antioxidant activities) have been described in patients with T1D. Hence, exploring HDL function, even in the presence of normal HDL-C levels, might provide additional insight into the underlying pathophysiology associated with increased CV risk in T1D. In the current review, we will provide a detailed overview of the current evidence for a role of HDL function as independent risk factor for the development of CVD in T1D. (C) 2017 Elsevier B.V. All rights reserve

Cotransfected human chondrocytes: over-expression of IGF-I and SOX9 enhances the synthesis of cartilage matrix components collagen-II and glycosaminoglycans

Damage to cartilage causes a loss of type II collagen (Col-II) and glycosaminoglycans (GAG). To restore the original cartilage architecture, cell factors that stimulate Col-II and GAG production are needed. Insulin-like growth factor I (IGF-I) and transcription factor SOX9are essential for the synthesis of cartilage matrix, chondrocyte proliferation, and phenotype maintenance. We evaluated the combined effect of IGF-I and SOX9 transgene expression on Col-II and GAG production by cultured human articular chondrocytes. Transient transfection and cotransfection were performed using two mammalian expression plasmids (pCMV-SPORT6), one for each transgene. At day 9 post-transfection, the chondrocytes that were over-expressing IGF-I/SOX9 showed 2-fold increased mRNA expression of the Col-II gene, as well as a 57% increase in Col-II protein, whereas type I collagen expression (Col-I) was decreased by 59.3% compared with controls. The production of GAG by these cells increased significantly compared with the controls at day 9 (3.3- vs 1.8-times, an increase of almost 83%). Thus, IGF-I/SOX9 cotransfected chondrocytes may be useful for cell-based articular cartilage therapies

Repair of ovine peripheral nerve injuries with xenogeneic human acellular sciatic nerves prerecellularized with allogeneic Schwann-like cells—an innovative and promising approach

Introduction: The iatrogenic effects of repairing peripheral nerve injuries (PNIs) with autografts (AGTs) encouraged the present study to involve a new approach consisting of grafting xenogeneic prerecellularized allogeneic cells instead of AGTs. Methods: We compared sheep's AGT regenerative and functional capacity with decellularized human nerves prerecellularized with allogeneic Schwann-like cell xenografts (onwards called xenografts). Mesenchymal stem cells were isolated from ovine adipose tissue and induced in vitro to differentiate into Schwann-like cells (SLCs). Xenografts were grafted in ovine sciatic nerves. Left sciatic nerves (20 mm) were excised from 10 sheep. Then, five sheep were grafted with 20 mm xenografts, and five were reimplanted with their nerve segment rotated 180° (AGT). Results: All sheep treated with xenografts or AGT progressively recovered the strength, movement, and coordination of their intervened limb, which was still partial when the study was finished at sixth month postsurgery. At this time, numerous intrafascicular axons were observed in the distal and proximal graft extremes of both xenografts or AGTs, and submaximal nerve electrical conduction was observed. The xenografts and AGT-affected muscles appeared partially stunted. Conclusions: Xenografts and AGT were equally efficacious in starting PNI repair and justified further studies using longer observation times. The hallmarks from this study are that human xenogeneic acellular scaffolds were recellularized with allogenic SCL and were not rejected by the nonhuman receptors but were also as functional as AGT within a relatively short time postsurgery. Thus, this innovative approach promises to be more practical and accessible than AGT or allogenic allografts and safer than AGT for PNI repair

Prevalence of morphological variations associated with femoroacetabular impingement according to age and sex: a study of 1878 asymptomatic hips in nonprofessional athletes

Background: Radiographic findings related to the cam and pincer variants of femoroacetabular impingement (FAI) include measurements of the alpha angle and lateral center-edge angle (LCEA). The function of these radiographic findings has been put into question because of high heterogeneity in reported studies. Purpose: The aim of this study was 3-fold: (1) to determine the prevalence of cam and pincer variants according to sex and age on anteroposterior (AP) pelvic radiographs from an asymptomatic nonathletic population, (2) to identify the most common radiographic signs of cam- and pincer-type variants, and (3) to determine if there are variations in the prevalence of these radiographic signs according to sex and age. Study design: Cross-sectional study; Level of evidence, 3. Methods: There were 3 independent observers who retrospectively analyzed the 939 AP pelvic radiographs (1878 hips) of patients aged 18 to 50 years who did not have hip symptoms and who were not professional athletes. The prevalence of the cam and pincer variants according to the alpha angle and LCEA, respectively, and the presence of other radiographic signs commonly associated with these variables were determined in the overall population and by subgroup according to sex and age group (18-30, 31-40, and 41-50 years). Descriptive and inferential statistics were used to analyze the study sample. Results: The mean age of the included population was 31.0 ± 9.2 years, and 68.2% were male. The prevalence of the cam-type variant was 29.7% (558/1878), and that of the pincer-type variant was 24.3% (456/1878). The radiographic signs that were most associated with the cam and pincer variants were a pistol-grip deformity and the crossover sign, respectively. Significant differences (P < .001) in the prevalence of these variants were identified between men and women in both variants. No differences were observed in the alpha angle or LCEA according to sex or age. Conclusion: Radiographic findings suggestive of FAI had significant variations with respect to sex and age in this study sample. This study provides information to determine the prevalence of these anatomic variants in the general population