Rheumatoid Arthritis Bone Fragility Is Associated With Upregulation of IL17 and DKK1 Gene Expression

Our aim was to compare bone gene expression in rheumatoid arthritis (RA) and primary osteoporosis (OP) patients. Secondary aims were to determine the association of gene expression of the Wnt/β-catenin signaling pathway with inflammatory cytokines in the bone microenvironment and to assess the serum levels of Wnt/β-catenin proteins in both groups. RA patients referred for hip replacement surgery were recruited. Primary OP patients were used as controls. Gene expression of Wnt pathway mediators, matrix proteins, and pro-inflammatory cytokines were analyzed in bone samples. Bone turnover markers, inflammatory cytokines, and Wnt mediators were measured in serum. Twenty-two patients were included: 10 with RA and 12 with primary OP. The expressions of Wnt10b (p?=?0.034), its co-receptor LRP6 (p?=?0.041), and its negative regulator DKK1 (p?=?0.008) were upregulated in RA bone. IL17 gene expression in bone was upregulated in RA patients (p?=?0.031) and correlated positively with Wnt10b (r?=?0.810, p?=?0.015), DKK2 (r?=?0.800, p?=?0.010), and RANKL/OPG ratio (r?=?0.762, p?=?0.028). DKK2 (p?=?0.04) was significantly decreased in RA serum compared with primary OP. In conclusion, bone fragility in RA patients is induced by an unbalanced bone microenvironment and is associated with a specific gene expression pattern, namely, the upregulation of IL17 and DKK1, suggesting that the modulation of these two pathways might prevent RA systemic bone loss.     

Creatine supplementation prevents acute strength loss induced by concurrent exercise

Purpose

To investigate the effect of creatine (CR) supplementation on the acute interference induced by aerobic exercise on subsequent maximum dynamic strength (1RM) and strength endurance (SE, total number of repetitions) performance.

Methods

Thirty-two recreationally strength-trained men were submitted to a graded exercise test to determine maximal oxygen consumption (VO_2max: 41.56 ± 5.24 ml kg^?1 min^?1), anaerobic threshold velocity (AT_v: 8.3 ± 1.18 km h^?1), and baseline performance (control) on the 1RM and SE (4 × 80 % 1RM to failure) tests. After the control tests, participants were randomly assigned to either a CR (20 g day^?1 for 7 days followed by 5 g day^?1 throughout the study) or a placebo (PL-dextrose) group, and then completed 4 experimental sessions, consisting of a 5-km run on a treadmill either continuously (90 % AT_v) or intermittently (1:1 min at vVO_2max) followed by either a leg- or bench-press SE/1RM test.

Results

CR was able to maintain the leg-press SE performance after the intermittent aerobic exercise when compared with C (p > 0.05). On the other hand, the PL group showed a significant decrease in leg-press SE (p ≤ 0.05). CR supplementation significantly increased bench-press SE after both aerobic exercise modes, while the bench-press SE was not affected by either mode of aerobic exercise in the PL group. Although small increases in 1RM were observed after either continuous (bench press and leg press) or intermittent (bench press) aerobic exercise in the CR group, they were within the range of variability of the measurement. The PL group only maintained their 1RM.

Conclusions

In conclusion, the acute interference effect on strength performance observed in concurrent exercise may be counteracted by CR supplementation.     

A putative role for homocysteine in the pathophysiology of acute bacterial meningitis in children

Background

Acute bacterial meningitis frequently causes cortical and hippocampal neuron loss leading to permanent neurological sequelae. Neuron death in acute bacterial meningitis involves the excessive activation of NMDA receptors and p53-mediated apoptosis, and the latter is triggered by the depletion of NAD?+?and ATP cellular stores by the DNA repair enzyme poly(ADP-ribose) polymerase. This enzyme is activated during acute bacterial meningitis in response to DNA damage induced, on its turn, by reactive oxygen and nitrogen species. An excess of homocysteine can also induce this cascade of events in hippocampal neurons.The present work aimed at investigating the possible involvement of homocysteine in the pathophysiology of meningitis by comparing its concentrations in cerebrospinal fluid (CSF) samples from children with viral or acute bacterial meningitis, and control individuals.

Methods

Homocysteine and cysteine concentrations were assessed by high-performance liquid chromatography in CSF samples from nine patients with acute bacterial meningitis, 13 patients with viral meningitis and 18 controls (median age: 4 years-old; range: <1 to 13) collected by lumbar puncture at admission at the Children's Hospital Joao Paulo II - FHEMIG, from January 2010 to November 2011.

Results

We found that homocysteine accumulates up to neurotoxic levels within the central nervous system of patients with acute bacterial meningitis, but not in those with viral meningitis or control individuals. No correlation was found between homocysteine and cysteine concentrations and the cerebrospinal fluid standard cytochemical parameters.

Conclusions

Our results suggest that HCY is produced intrathecally in response to acute bacterial meningitis and accumulates within the central nervous system reaching potentially neurotoxic levels. This is the first work to propose a role for HCY in the pathophysiology of brain damage associated with acute bacterial meningitis.

     

Enzyme replacement therapy in juvenile glycogenosis type II: a longitudinal study

Glycogenosis type II, a genetic muscle-wasting disorder, results in a spectrum of clinical phenotypes. Enzyme replacement therapy is effective in the infantile form of the disease, while little is known about its effectiveness in late-onset disease, especially in juvenile patients. The purpose of this retrospective cohort study was to assess the long-term effects of enzyme replacement therapy (ERT) in juvenile glycogenosis type II (GSDII). Eight Italian juvenile GSDII patients, receiving biweekly infusions of 20 mg/kg recombinant human α-glucosidase for at least 72 months, were enrolled (median age at therapy start was 11.8 years). Six-minute walk test (6MWT) and forced vital capacity (FVC), measured in upright position, were chosen as the principal outcome measures. Global motor disability (modified Walton scale (WS)), muscle enzymes levels [creatine phosphokinase (CK), lactate dehydrogenase (LDH), aspartate transaminase (AST), alanine transaminase (ALT)] and body mass index (BMI) were also analysed both at baseline (therapy start) and annually afterwards. At baseline, most patients (six out of eight) did not show muscle function impairment (WS?≤?2). The performance at 6MWT showed a slight improvement during follow-up as well as FVC. Muscle enzymes levels showed a clear decrease after the 1st year of treatment while remained stable afterwards. An overall decrease in BMI was also observed during follow-up, although at the individual level, trends were variable. Conclusion: ERT is effective in stabilising both motor and lung functions in juvenile patients with GSDII, possibly slowing down the rate of disease progression. Randomised controlled trials are needed to understand whether early treatment allows juvenile patients to reach adulthood with a more beneficial residual muscular function than untreated patients.     

Safety and tolerance of a new extensively hydrolyzed rice protein-based formula in the management of infants with cow’s milk protein allergy

Guidelines recommend the use of extensively hydrolyzed cow’s milk protein-based formulas (eHF) in the treatment of infants with cow’s milk protein allergy (CMPA). Extensively hydrolyzed rice protein infant formula (eRHF) has recently become available and could offer a valid alternative. A prospective trial was performed to evaluate the hypo-allergenicity and safety of a new eRHF in infants with a confirmed CMPA. Patients were fed the study formula for 6 months. Clinical tolerance of the eRHF was evaluated with a symptom-based score (SBS) and growth (weight and length) was monitored. Forty infants (mean age, 3.4 months; range, 1–6 months) with CMPA confirmed by a food challenge were enrolled. All infants tolerated the eRHF and the SBS significantly decreased as of the first month of intervention. Moreover, the eRHF allowed a catch-up to normal weight gain as of the first month as well as a normalization of the weight-for-age, weight-for length, and BMI z-scores within the 6-month study period. Conclusion: In accordance with current guidelines, this eRHF was tolerated by more than 90 % of children with proven CMPA with a 95 % confidence interval. This eRHF is an adequate and safe alternative to cow milk-based eHF.     

“Baby Heart Project”: The Italian Project for Accreditation and Quality Management in Pediatric Cardiology and Cardiac Surgery

Optimization of the relationship between the supply and the demand for medical services should ideally be taken into consideration for the planning within each national Health System. Although government national health organizations embrace this policy specifically, the contribution of expert committees (under the scientific societies’ guarantee in any specific medical field) should be advocated for their capability to collect and analyze the data reported by the various national institutions. In addition, these committees have the competence to analyze the need for the resources necessary to the operation of these centers. The field of pediatric cardiology and cardiac surgery may represent a model of clinical governance of particular interest with regard to programming and to a definition of the quality standards that may be extended to highly specialized institutions and ideally to the entire Health System. The “Baby Heart Project,” which represents a model of governance and clinical quality in the field of pediatric cardiology and cardiac surgery, was born from the spontaneous aggregation of a committee of experts, supported by duly appointed Italian Scientific Societies and guided by a national agency for accreditation. The ultimate aim is to standardize both procedures and results for future planning within the national Health System.     

Assessment of Color Stability of White Mineral Trioxide Aggregate Angelus and Bismuth Oxide in Contact with Tooth Structure

Introduction

Dental discoloration with use of materials containing bismuth oxide has been reported. It is postulated that the discoloration is a result of chemical interaction of bismuth oxide with dentin. The aim of the study was to analyze dental color alteration and the chemical interaction of bismuth oxide with the main components present in composite (methacrylate) and in dentin (collagen).

Methods

Fifty bovine teeth were prepared and filled with white mineral trioxide aggregate (MTA) Angelus, Portland cement (PC) with 20% zirconium oxide, or PC with 20% calcium tungstate and then sealed with composite. Triple antibiotic paste and unfilled samples were the positive and negative controls, respectively. The specimens were stored in separate flasks immersed in tap water at 37°C with ambient light blocked out. The color assessment was performed with a spectrophotometer at different intervals, namely before filling and 24 hours, 15 days, and 30 days after filling. The color change and the luminosity were calculated. The statistical analysis was performed by using nonparametric Kruskal-Wallis and Dunn tests (P < .05). The interaction of the bismuth oxide, zirconium oxide, and calcium tungstate with collagen and methacrylate was assessed by placing the materials in contact, followed by color assessment.

Results

The analysis of color change values showed that all the materials presented color alteration after the evaluated periods. Statistically higher luminosity was verified for PC/20% zirconium oxide in comparison with white MTA Angelus (P < .05). The teeth filled with white MTA Angelus demonstrated a grayish discoloration with evident dentin staining. Bismuth oxide exhibited a color change when in contact with collagen.

Conclusions

The color of white MTA Angelus was altered in contact with dental structures. Collagen, which is present in dentin matrix, reacted with bismuth oxide, resulting in a grayish discoloration. The use of an alternative radiopacifier to replace bismuth in white MTA is indicated.     

Intermittent Parathyroid Hormone Administration Improves Periodontal Healing in Rats

Background: Intermittent administration of parathyroid hormone (PTH) promotes new bone formation in patients with osteoporosis and bone fractures. It was shown previously that PTH also reduces periodontitis‐related bone loss. The aim of this study is to evaluate the effect of treatment with PTH on periodontal healing in rats. Methods: Fenestration defects were created at the buccal surface of the distal root of the mandibular first molars, and both periodontal ligament (PDL) and cementum were removed. Animals were then assigned to two groups (eight animals per group): group 1: control, placebo administration; and group 2: test, human PTH (hPTH) 1‐34 administration at a concentration of 40 μg/kg. For both groups, the animals were injected every 2 days, and the animals were sacrificed at 14 and 21 days after surgery. Specimens were harvested and processed for routine decalcified histologic sections. The following parameters were assessed: 1) remaining bone defect extension (RBDE); 2) newly formed bone density (NFBD); 3) total callus area (TCA); 4) osteoclast number (ON) in the callus region; and 5) newly formed dental cementum‐like tissue (NFC). Birefringence of root PDL reattachment was also evaluated. Results: Birefringence analysis showed root PDL reattachment for both groups 21 days after treatment. Intermittent hPTH 1‐34 administration decreased RBDE (P <0.01) and increased NFBD (P <0.01), TCA (P <0.01), area of NFC (P <0.01), and ON in the callus region (P <0.01). Conclusion: Within the limits of the present study, intermittent administration of hPTH 1‐34 led to an enhanced periodontal healing process compared with non‐treated animals.     

A Retrospective Evaluation of the Survival Rates of Splinted and Non‐Splinted Short Dental Implants in Posterior Partially Edentulous Jaws

Background: The aim of the present study is to evaluate the survival rate and bone loss around short implants (≤10 mm) supporting splinted or non‐splinted posterior prostheses during a follow‐up period of 3 to 16 years. Methods: A total of 453 implants from 198 patients was divided into splinted or non‐splinted groups. Implant survival rate was calculated for each group, and potential risk was represented as odds ratio (OR). The final linear distance from implant platform level to the first bone‐to‐implant contact was compared to this same reference just after loading by digital periapical radiographs to determine the marginal bone loss (BL). Results: The splinted group comprised 219 implants in 86 patients, whereas the non‐splinted group included 234 implants from 112 patients. The mean follow‐up period was 9.7 ± 3.7 years. Although different success rates were found for splinted (97.7%) and non‐splinted (93.2%) groups, they exhibited similar BL (1.22 ± 0.95 mm and 1.27 ± 1.15 mm, respectively). The success of splinted implants was associated with no other variable, whereas non‐splinted implants exhibited higher risk of failure when placed in men (OR = 3.2) and when implants shorter than 10 mm were used (OR = 3.6 and 4.1 for 8.5 mm and 7 mm, respectively). Regardless of group, 71.4% of the unsuccessful implants failed before the end of the first year after loading. Conclusion: Non‐splinted posterior short implants had a somewhat lower success rate than splinted short implants, and the failure rate in non‐splinted short implants appeared to be greater in males as well as in implants ≤10 mm.     

Surface structure and mechanical properties of impaction-modified Y-TZP

Objectives

The objectives of the study were to describe the surface structure and the chemical surface composition of Y-TZP ceramics produced by using the modified additive technique and to evaluate the flexural strength of Y-TZP with or without surface modification and with different pretreatments: etching before or after sintering combined with or without an adhesive cement system.

Methods

Y-TZP discs were used for surface analysis (n = 48) and for biaxial flexural strength testing (n = 200). The specimens were divided into groups depending on the cementation surface of Y-TZP: unmodified, sandblasted or glass-modified Y-TZP surfaces, and according to the production process: etching before or after sintering.

Results

The surface structure and the chemical composition of glass-modified Y-TZP differ; a rougher surface and phase transformation was identified compared to unmodified Y-TZP.The unmodified Y-TZP groups showed significantly higher flexural strength compared to the glass-modified groups (p < 0.001) and showed increased flexural strength after sandblasting (p < 0.001). Furthermore, by adding cement to the surface, the value increased even further in comparison with the sandblasted non-cemented specimens (p < 0.01). After thermocycling, however, the cement layer on the unmodified and the sandblasted surfaces had air pockets and regions with loose cement.

Significance

A rougher surface structure, superficial glass remnants and a higher content of m-phase was present in the cementation surface of glass-modified Y-TZP. The glass modification creates a bondable cementation surface that is durable. By etching the glass-modified Y-TZP before sintering, a more homogenous surface is created compared to one that is etched after sintering.