Chemokine ligand 2 and paraoxonase-1 in non-alcoholic fatty liver disease:The search for alternative causative factors

The incidence and prevalence of non-alcoholic fatty liver disease(NAFLD)is constantly increasing.Despite this is apparently associated with the growing increase in obesity,insulin resistance and obesity-related metabolic disturbances their presence is not a necessary or sufficient condition to explain the accumulation of fatin the liver.Conversely,NAFLD is a predictor of other metabolic risks.NAFLD is currently the most frequent chronic liver disease but should not be considered benign or anecdotic because a considerable proportion of patients with NAFLD progress to cirrhosis and endstage liver disease.Consequently,the search for alternative molecular mechanisms with therapeutic implications in NAFLD and associated disorders deserves a careful consideration.Mitochondria are possible targets as these organelles generate energy from nutrient oxidation.Some findings,generated in patients with extreme obesity and in murine models,support the notion that NAFLD could be a mitochondrial disease.This is plausible because mitochondrial dysfunction affects the accumulation of lipids in hepatocytes and promotes lipid peroxidation,the production of reactive oxygen species,the release of cytokines causing inflammation and cell death.Here we discuss basic research and mechanistic studies targeting the role of chemokine ligand 2 in liver inflammation and that of the paraoxonases in the oxidative stress.Their combination and association with mitochondrial dysfunction may uncover mechanisms underlying the progression of NAFLD and may help to identify novel therapeutic targets.     

Effect of implant macro-design on primary stability: A prospective clinical study

Background

Implant restorations have become a high predictable treatment option. Several caracteristics such as surgical technique and implant design can influence the treatment outcomes. The aim of the present study was to evaluate the influence of implant macro-design on primary stability measured with resonance frequency analysis (RFA) and insertion torque (IT).

Material and Methods

A total of 47 implants divided in two groups: Test group (TI): 22 Tapered MIS® Seven implants; Control group (CI): 25 cylindrical Astra® Osseospeed implants. All implants were inserted following the manufacturers’ standard protocols. Implant primary stability was measured at the moment of implant placement by registering insertion torque values (ITv) and ISQ values by means of Osstell™ Mentor (ISQv) (Integration Diagnostic Ltd., Goteborg, Sweden).

Results

In the mandible, mean ISQv for tapered implants (TI) was 71.67±5.16 and for cylindrical implants (CI) 57.15±4.83 (p=0.01). Mean insertion torque was 46.67±6.85 Ncm for TI and 35.77±6.72 Ncm for CI (p=0.01). In the maxilla, mean ISQ was 67.2±4.42 for tapered implants and 49.17±15.30 for cylindrical implants (p=0.01). Mean insertion torque for TI was 41.5±6.26 Ncm and for CI 39.17±6.34 Ncm (p>0.05). For tapered implants, no correlation could be found between implant diameter and primary stability. But for cylindrical implants there was a statistically significant correlation between implant diameter and primary stability: ITv (p=0.03); ISQv (p=0.04).

Conclusions

Within the limits of the present study, tapered shaped implants achieve higher primary stability measured through ISQ and insertion torque values. Moreover, for cylindrical implants positive correlation has been established between implant diameter and primary stability. Key words:Primary stability, tapered, cylindrical, conical, implant macro-design.     

Molecular composition of the alveolar lining fluid in the aging lung

As we age, there is an increased risk for the development of pulmonary diseases, including infections, but few studies have considered changes in lung surfactant and components of the innate immune system as contributing factors to the increased susceptibility of the elderly to succumb to infections. We and others have demonstrated that human alveolar lining fluid (ALF) components, such as surfactant protein (SP)-A, SP-D, complement protein C3, and alveolar hydrolases, play a significant innate immune role in controlling microbial infections. However, there is a lack of information regarding the effect of increasing age on the level and function of ALF components in the lung. Here we addressed this gap in knowledge by determining the levels of ALF components in the aging lung that are important in controlling infection. Our findings demonstrate that pro-inflammatory cytokines, surfactant proteins and lipids, and complement components are significantly altered in the aged lung in both mice and humans. Further, we show that the aging lung is a relatively oxidized environment. Our study provides new information on how the pulmonary environment in old age can potentially modify mucosal immune responses, thereby impacting pulmonary infections and other pulmonary diseases in the elderly population.     

A nonsense polymorphism in the protein Z-dependent protease inhibitor increases the risk for venous thrombosis

The protein Z-dependent protease inhibitor (ZPI) is a hemostatic serpin with anticoagulant activity. As for antithrombin, deficiency of ZPI could have relevant thrombotic consequences. We have studied 6 genetic modifications affecting the ZPI gene, identifying 5 haplotypes. Haplotype H5 is featured by a stop codon at position 67. The relevance of these genetic modifications and haplotypes in venous thrombosis was evaluated in a case-control study including 1018 patients and 1018 age- and sex-matched controls. Surprisingly, the H5 haplotype was found in 0.9% of controls, supporting that the Arg67Stop change is a low frequency nonsense polymorphism. The prevalence of this haplotype increased significantly in patients (3.0%), one of whom was in a homozygous state. Multivariate analysis confirms that carriers have a 3.3-fold risk of developing venous thrombosis (P = .002; 95% CI: 1.5-7.1). Moreover, we observed a significant association of this polymorphism with familial history of thrombosis (P < .001). Our study supports that the ZPI Arg67Stop nonsense polymorphism might be an independent genetic risk factor for venous thrombosis. This polymorphism has slightly lower prevalence but similar thrombotic risk than the FV Leiden or prothrombin 20210A. Although further studies are required, all available data support that the ZPI is a candidate to play a significant role in thrombosis and should be evaluated in thrombophilic studies.     

Improvement to the Corrosion Resistance of Ti-Based Implants Using Hydrothermally Synthesized Nanostructured Anatase Coatings

The electrochemical behavior of polycrystalline TiO₂ anatase coatings prepared by a one-step hydrothermal synthesis on commercially pure (CP) Ti grade 2 and a Ti13Nb13Zr alloy for bone implants was investigated in Hank’s solution at 37.5 °C. The aim was to verify to what extent the in-situ-grown anatase improved the behavior of the substrate in comparison to the bare substrates. Tafel-plot extrapolations from the potentiodynamic curves revealed a substantial improvement in the corrosion potentials for the anatase coatings. Moreover, the coatings grown on titanium also exhibited lower corrosion-current densities, indicating a longer survival of the implant. The results were explained by considering the effects of crystal morphology, coating thickness and porosity. Evidence for the existing porosity was obtained from corrosion and nano-indentation tests. The overall results indicated that the hydrothermally prepared anatase coatings, with the appropriate morphology and surface properties, have attractive prospects for use in medical devices, since better corrosion protection of the implant can be expected.     

Enfermedades inflamatorias mediadas por inmunidad en pacientes con enfermedad inflamatoria intestinal. Datos basales del estudio Aquiles

Objective

To determine the prevalence of immune-mediated inflammatory diseases (IMID) in a cohort of patients with inflammatory bowel disease (IBD) enrolled in hospital gastroenterology outpatients units for the AQUILES study, a prospective 2-year follow-up study.

Material and methods

We included patients ≥ 18 years old with a prior or new diagnosis of IBD (Crohn disease [CD], ulcerative colitis [UC] or indeterminate colitis). Diagnoses were collected in a cross-sectional manner from the clinical records at enrollment of a new patient in the study.

Results

We included 526 patients (mean age 40.2 years; 47.3% men, 52.7% women), 300 with CD (57.0%), 218 with UC (41.4%) and 8 with indeterminate colitis. Other types of IMID were present in 71 patients (prevalence: 13.5%, 95% CI: 10.8-16.7): 47 were spondyloarthropathies (prevalence: 8.9%); 18 psoriasis (3.4%); 5 pyoderma gangrenosum (1.0%), and 11 uveitis (2.1%). The prevalence of IMID was higher in patients with CD than in those with UC (17.0% [95% CI: 13.2-21.7] vs 9.2% [95% CI: 6.0-13.8], p = 0.011). In the multivariate analysis, the variables associated with the presence of IMID were diagnosis of CD (OR = 1.8 [95% CI: 1.1-3.2]) and duration of IBD ≥ 4 years (OR = 2.1 [95% CI: 1.1-4.1] in those with disease duration 4-8 years, and OR = 2.1 [95% CI: 1.2-3.9] in those with ≥ 8 years vs. < 4 years).

Conclusions

In the cohort of patients with IBD in the AQUILES study, 13.5% had another IMID, with a higher prevalence in patients with CD and > 4 years since disease onset.     

Allogeneic stem cell transplantation in AML with t(6;9)(p23;q34);DEK-NUP214 shows a favourable outcome when performed in first complete remission

Acute myeloid leukaemia (AML) with t(6;9)(p23;q34) is a poor-risk entity, commonly associated with FLT3-ITD (internal tandem duplication). Allogeneic stem-cell tranplantation (allo-SCT) is recommended, although studies analysing the outcome of allo-SCT in this setting are lacking. We selected 195 patients with t(6;9) AML, who received a first allo-SCT between 2000 and 2016 from the EBMT (European Society for Blood and Marrow Transplantation) registry. Disease status at time of allo-SCT was the strongest independent prognostic factor, with a two-year leukaemia-free survival and relapse incidence of 57% and 19% in patients in CR1 (first complete remission), 34% and 33% in CR2 (second complete remission), and 24% and 49% in patients not in remission, respectively (P < 0·001). This study, which represents the largest one available in t(6;9) AML, supports the recommendation to submit these patients to allo-SCT in CR1.     

Roughness and bonding strength of bioactive apatite layer on dental implants

This study examined the roughness and bonding strength of the chemical-made apatite layer in comparison with the titanium surface and the plasma-sprayed apatite. Commercially pure titanium plates were heated and chemically treated to deposit crystalline apatite on their surface. The roughness of the titanium surface of the original samples and the apatite surface was analyzed by a roughness surface tester. A scratch test was used to compare the adhesion of the chemical apatite layer to the titanium with the adhesion of a plasma-sprayed layer. A dense bone-like apatite layer was formed on the surface of the titanium by a simple chemical method. The surface roughness test showed that the chemical apatite coating increased the roughness of the samples. The scratch test showed that the bonding strength of the chemical-made apatite coatings to the titanium substrate was higher than the plasma-sprayed apatite coatings. The apatite layer produced by chemical treatment did not show a lower roughness than the titanium substrate. This chemical apatite layer also bonded tighter to the titanium than the plasma-sprayed apatite. This chemically made apatite coating is expected to provide a long-term implant-bone fixation.