Effects of hedgehog proteins on tissue engineering of cartilage in vitro

The effects of three derivatives of the N-terminal signaling domain of hedgehog proteins on cartilage engineered in vitro were investigated, with specific focus on the ability to increase tissue growth rate and concentrations of major extracellular matrix components, that is, glycosaminoglycans (GAG) and collagen, and on the effects on morphological appearance of the tissue. Bovine articular chondrocytes were cultured on biodegradable polyglycolic acid (PGA) scaffolds with or without the addition of dipalmitoylated sonic hedgehog (dp-shh), dipalmitoylated indian hedgehog (dp-ihh), or sonic hedgehog dimer (shh-dimer) to medium with either 1% or 10% fetal bovine serum (FBS). All three hedgehog proteins dose-dependently increased construct weights (by up to 1.95-fold, dp-shh at 1,000 ng/mL) and the fraction of GAG over 4 weeks (by up to 2.7-fold, dp-shh at 1,000 ng/mL), as compared to control constructs. Dp-shh and dp-ihh elicited similar responses; a 10-fold higher concentration of nonacylated shh-dimer was necessary to reach comparable results. Positive hedgehog effects were more pronounced in medium containing 1% FBS than in medium containing 10% FBS; however, at either FBS concentration, cartilaginous tissues grown in the presence of hedgehog proteins appeared morphologically more mature. Hedgehog derivatives thus appear as promising candidates to improve the development and composition of engineered cartilage.     

Lumbopelvic sagittal standing posture associations with anthropometry,physical activity levels and trunk muscle endurance in healthy adults

Background:Various factors, inherited and acquired, are associated with habitual spinal postures.Objective:The purpose of this study was to identify the relationships between trunk muscle endurance, anthropometry and physical activity/inactivity and the sagittal standing lumbopelvic posture in pain-free young participants.Methods:In this study, 112 healthy young adults (66 females), with median (IQR) age of 20 years (18.2–22 years), without low back pain, injury or trauma were included. Lumbar curve (LC) and sacral slope (SS) angles were measured in standing with a mobile phone application (iHandy level). Anthropometric, physical activity/inactivity levels (leisure-time sport involvement and sitting hours/day) and abdominal (plank prone bridge test) and paraspinal (Sorensen test) isometric muscle endurance measures were collected.Results:LC and SS angles correlated significantly (r=0.80, p<0.001). Statistically significant differences for both LC (p=0.023) and SS (p=0.013) angles were identified between the male and female participants. A significant negative correlation was identified between the abdominal endurance time and LC (r=−0.27, p=0.004); however, the power of this result (56%) was not sufficiently high. The correlation between abdominal endurance and SS was non-significant (r=−0.17, p=0.08). In addition, no significant associations were identified between either of the sagittal lumbopelvic angles (LC–SS) in standing and the participants’ body mass index (BMI), paraspinal endurance, leisure-time sport involvement or sitting hours/day.Conclusion:The potential role of preventive exercise in controlling lumbar lordosis via enhancement of the abdominal muscle endurance characteristics requires further confirmation. A subsequent study, performed in a larger population of more diverse occupational involvement and leisure-time physical activity levels, is proposed.     

Prevalence of hypertension and cardiovascular risk factors among long‐term AIDS survivors: A report from the field

HIV infection is associated with increased risk and progression of cardiovascular disease (CVD), yet little is known about the prevalence of CVD risk factors among long‐term AIDS survivors in resource‐limited settings. Using routinely collected data, we conducted a retrospective study to describe the prevalence of CVD risk factors among a cohort of HIV‐infected patients followed for over 10 years in Port‐au Prince, Haiti. This cohort includes 910 adults who initiated antiretroviral therapy (ART) between 2003 and 2004 and remained in care between 2014 and 2016 when routine screening for CVD risk factors was implemented at a large clinic in Haiti. A total of 397 remained in care ≥10 years and received screening. At ART initiation, 59% were female, median age was 38 years (IQR 33‐44), and median CD4 count was 117 cells/mm³ (IQR 34‐201). Median follow‐up time from ART initiation was 12.1 years (IQR 11.7‐12.7). At screening, median CD4 count was 574 cells/mm³ (IQR 378‐771), and 84% (282 of 336 screened) had HIV‐1 RNA < 1000 copies/mL. Seventy‐four percent of patients had at least 1 risk factor including 58% (224/385) with hypertension, 8% (24/297) diabetes, 43% (119/275) hypercholesterolemia, 8% (20/248) active smoking, and 10% (25/245) obesity. Factors associated with hypertension were age (adjusted OR 1.06, P < .001) and weight at screening (adjusted OR 1.02, P = .019). Long‐term AIDS survivors have a high prevalence of CVD risk factors, primarily hypertension. Integration of cardiovascular screening and management into routine HIV care is needed to maximize health outcomes among aging HIV patients in resource‐limited settings.     

HERV-K(HML-2) GAG/ENV antibodies as indicator for therapy effect in patients with germ cell tumors

Germ cell tumors (GCT) are strictly associated with the expression of HERV-K(HML-2) proviruses, and the majority of GCT patients produce antibodies to structural proteins of these proviruses. The objective of our study was to determine the significance of the serological response to HERV-K(HML-2) Gag and Env proteins for diagnosis, management of GCT patients and estimation of the therapy success. The data document a strong association of HERV-K(HML-2) antibodies and the clinical manifestation of the disease and therapy success. HERV-K(HML-2) antibodies seem to have an important diagnostic value as well as indicator of chemotherapy success.     

In Situ Gene Expression Analysis During BMP2-induced Ectopic Bone Formation in Mice Shows Simultaneous Endochondral and Intramembranous Ossification

We examined the molecular progression of ectopic bone development upon application of recombinant human bone morphogenetic protein-2 (rhBMP2), using a commercial collagen type I carrier, in the hind quarter muscles of mice. We performed a gene expression study using mRNA in situ hybridisation to compare embryonic cartilage and bone formation with BMP2-induced ectopic bone formation. As bone growth can be induced postnatally or in adult animals, we examined the expression of molecules regulating embryonic bone development. We found that the mRNAs of the same molecules, such as Indian hedgehog (IHH), parathyroid hormone (PTH)/PTH-related peptide receptor (PPR) and BMPs, that regulate embryonic cartilage and bone development, are expressed during BMP-induced ectopic bone formation, suggesting parallels in the mechanisms controlling these processes. Our studies support by molecular means the previous findings in rats that BMP2-induced ectopic bone formation in mice undergoes bone development involving both modes, endochondral and intramembranous ossification, simultaneously at different sites of the implant.     

Insertion of central venous catheters for hemodialysis using angiographic techniques in patients with previous multiple catheterizations

Introduction

Central venous catheter placement is an effective alternative vascular access for dialysis in patients with chronic renal failure. The purpose of this study was to evaluate the insertion of central venous catheters for hemodialysis using angiographic techniques in patients with previous multiple catheterizations in terms of efficacy of the procedure and early complications.

Materials and methods

Between 2008 and 2010, the vascular access team of our hospital placed 409 central venous catheters in patients with chronic renal failure. The procedure was performed using the Seldinger blind technique. In 18 (4.4%) cases it was impossible to advance the guidewire, and so the patients were transported to the angiography suite.

Results

Using the angiographic technique, the guidewire was advanced in order to position the central venous catheter. The latter was inserted into the subclavian vein in 12 (66.6%) cases, into the internal jugular vein in 4 (22.2%) and into the femoral vein in 2 (11.1%) cases. There was only one complicated case with severe arrhythmia in 1 (5.5%) patient.

Conclusion

Our results suggest that insertion of central venous catheters using angiographic techniques in hemodialysis patients with previous multiple catheterizations is a safe and effective procedure with few complications and high success rates.     

Pathogenicity of a human thyroglobulin peptide (2340-2359) in mice with high or low genetic susceptibility to thyroiditis

We have previously identified a 20-mer peptide of human thyroglobulin (hTg), p2340 (aa2340-2359), which induced experimental autoimmune thyroiditis (EAT) in AKR/J (H-2(k)) and HLA-DR3 transgenic mice. In this study, we investigated the thyroiditogenic potential of p2340 in 'high responder' CBA/J (H-2(k)) and SJL/J (H-2(s)) or 'low responder' C57BL/6 (H-2(b)) and BALB/c (H-2(d)) mice. Mice were immunized subcutaneously with 100 nmol of p2340 in complete Freund's adjuvant (CFA) and both the proliferative capacity of their lymph node cells in the presence of p2340 or intact Tg and the production of peptide-specific antibodies were investigated. The p2340 peptide was found to contain B-cell and non-dominant T-cell epitope(s) in all strains tested. Moreover, it elicited EAT in CBA/J (2/6, infiltration index (I.I.) 1) and SJL/J (5/5, I.I. 1-3) mice after direct challenge and in BALB/c (4/7, I.I. 1) and C57BL/6 (1/5, I.I. 1) after adoptive transfer of p2340-primed lymph node cells. P2340 is the first Tg peptide found to be pathogenic in low as well as high responder mouse strains and thus will allow us to investigate mechanisms of EAT induction in a genetically resistant host.