Frequency of serological markers of rheumatoid arthritis in patients with IgA anti‐β2 glycoprotein I antibodies

AimTo determine the frequency of serological markers of RA in patients with anti‐β2 glycoprotein I antibodies (aβ2GPI) of IgA isotype.Material and MethodsA retrospective study was conducted on 67 patients with aβ2GPI‐IgA. Ninety healthy blood donors (HBD) were used as a control group. IgG anti‐cyclic citrullinated peptides antibodies (CCP‐Ab) and rheumatoid factors (RF) IgG, IgA, and IgM were detected by enzyme‐linked immunosorbent assay (ELISA).ResultsSeventeen patients and eight HBD had CCP‐Ab and/or RF (25.4% vs. 8.9%, p = 0.005, CI 95% [14.95; 35.79], odds ratio = 3.5). The frequency of CCP‐Ab was significantly higher in patients than in healthy subjects (14.9% vs. 3.3%, p = 0.009). IgA isotype of RF was significantly higher in patients than in controls (7.5% vs. 0%, p = 0.02). In male patients, CCP‐Ab and/or RF were more frequent than in healthy male subjects (37.5% vs. 11.8%, p = 0.02). In patients, no correlation was found between the levels of aβ2GPI‐IgA and CCP‐Ab (r = 0.082, p = 0.51). There was no correlation between the level aβ2GPI‐IgA and the level of the isotypes of RF (IgG, IgA, and IgM) in patients (r = 0.1, p = 0.37; r = 0.17, p = 0.17 and r = 0.07, p = 0.59 respectively).ConclusionFrequencies of CCP‐Ab and RF are high in patients with aβ2GPI‐IgA suggesting that these patients are susceptible to developing RA.     

EPIDEMIOLOGIE DE L’HYPERTENSION ARTERIELLE EN TUNISIE.Etude Hammam Sousse/Sahloul Heart Study (HSHS)

Introduction: Tunisia is experiencing a double burden of morbidity, characterized by the explosion of cardiovascular diseases and their risk factors including arterial Hypertension. The objective of this study, based on the HSHS cohort (Hammam Sousse Sahloul Heart Study), was to determine the prevalence of hypertension in the general population and to identify its predisposing factors. Methods: HSHS is a cardiovascular health promotion initiative in the city of Hammam Sousse (Tunisia). The study was conducted via a random sample of households, using the WHO PEV technique, made up of 33 clusters, of 33 households each. All people aged 20 and over, included, benefited from a questionnaire, a physical examination and a biological assessment. The Systolic Blood Pressure (SBP) and the Diastolic Blood Pressure (DBP) were measured from the average of the last two measurements, by an OMRON type tensiometer, of suitable width. These prevalences were adjusted according to sex and age group, by their weighting coefficients in the general population, and they were accompanied by their 95% CIs. Binary logistic regression was conducted to identify independent factors associated with hypertension. Results: The study population was composed of 481 men (33.4%) and 960 women (66.6%), with an average age of 49.6±16.35 years in males (M) and 46.6±16.18 in females (F). In addition to the family history of hypertension, the sufficient weekly consumption of vegetables and fruits was low (M: 32.4%, F: 24.9%). The adjusted rate of hypertension in the adult study population was 32.5%, 95%CI[31.9-33.1] (M: 36.4%, 95%CI[35, 5-37.3]; F: 28.4%; 95% CI[27.6-29.2]), reaching in the age group of 60 years and above: M: 74.6% (95%CI[66.9-82.3], F: 82.7% (95%CI[73.8-83.6]) Multivariate analysis identified five independent factors significantly associated with hypertension: male sex (ORa=1.55 [1.18-2.03]), age over 40 years (ORa=6.54[4.70-9.11]), low level of schooling (ORa=1.80 [1.36-2.38]), low physical activity (ORa=1.42[1.07-1.88]) and high socio-economic level (ORa=1 .84 [1.30-2.63]). Conclusion: The HSHS study confirmed the high prevalence of hypertension, and the extent of its low detection and control. Hence the need for a universal approach to health promotion, oriented towards the general population, piloted by its local organizations, based on the adoption of a healthy lifestyle, and centered on physical activity.     

Development and characterization of a new chitosan-based scaffold associated with gelatin,microparticulate dentin and genipin for endodontic regeneration

ObjectiveAn ideal scaffold for endodontic regeneration should allow the predictableness of the new tissue organization and limit the negative impact of residual bacteria. Therefore, composition and functionalization of the scaffold play an important role in tissue bioengineering. The objective of this study was to assess the morphological, physicochemical, biological and antimicrobial properties of a new solid chitosan-based scaffold associated with gelatin, microparticulate dentin and genipin.MethodsScaffolds based on chitosan (Ch); chitosan associated with gelatin and genipin (ChGG); and chitosan associated with gelatin, microparticulate dentin and genipin (ChGDG) were prepared by using the freeze-drying method. The morphology of the scaffolds was analyzed by scanning electron microscopy (SEM). The physicochemical properties were assessed for biodegradation, swelling and total released proteins. The biological aspects of the scaffolds were assessed using human cells from the apical papilla (hCAPs). Cell morphology and adhesion to the scaffolds were evaluated by SEM, cytotoxicity and cell proliferation by MTT reduction-assay. Cell differentiation in scaffolds was assessed by using alizarin red assay. The antimicrobial effect of the scaffolds was evaluated by using the bacterial culture method, and bacterial adhesion to the scaffolds was observed by SEM.ResultsAll the scaffolds presented porous structures. The ChCDG had more protein release, adhesion, proliferation and differentiation of hCAPs, and bacteriostatic effect on Enterococcus faecalis than Ch and ChGG (p < 0.05).SignificanceThe chitosan associated with gelatin, microparticulate dentin and genipin has morphological, physicochemical, biological and antibacterial characteristics suitable for their potential use as scaffold in regenerative endodontics.     

Localization and determination of infarct size by Gd-Mesoporphyrin enhanced MRI in dogs

Background: Accurate localization and sizing of a myocardial infarction are necessary for clinical decision making and even more in research. Gd-Mesoporphyrin enhanced magnetic resonance imaging (MRI) was recently shown to specifically delineate necrosis in liver tumors, renal and muscle necrosis and myocardial infarction in rats. In this study, we investigated this technique's potential to accurately delineate myocardial infarction in a larger animal species, the dog. Methods: Myocardial infarction was induced in 8 dogs by ligation of the left anterior descending coronary artery, 4 of which were reperfused after 3 hr. Gd-Mesoporphyrin (0.05 mmol/kg) was injected intravenously 210 min after the onset of ischemia (n = 6) or after 24 hr in 2 dogs with non-reperfused infarctions. MRI was performed 10 hr. after administration of Gd-Mesoporphyrin. In vivo MRI consisted of EKG-triggered, respiratory gated T1-weighted spin echo and segmented turboFLASH long and short axis measurements. Post-mortem, a spin echo short axis measurement was repeated. Infarct size was determined planimetrically by TTC staining of left ventricular slices. Results: In all instances, there was a very close qualitative agreement between the MRI and TTC defined myocardial infarction. Quantitatively, the linear regression from post-mortem MRI to TTC determined infarct size yielded a result very close to the line of identity (regression coefficient: 0.980 ± 0.026, p<0.000001, adjusted R² = 0.964). Conclusion: We conclude that Gd-Mesoporphyrin enhanced MRI is a promising tool for the accurate delineation of myocardial infarction.     

Delaying aging and the aging-associated decline in protein homeostasis by inhibition of tryptophan degradation

Toxicity of aggregation-prone proteins is thought to play an important role in aging and age-related neurological diseases like Parkinson and Alzheimer's diseases. Here, we identify tryptophan 2,3-dioxygenase (tdo-2), the first enzyme in the kynurenine pathway of tryptophan degradation, as a metabolic regulator of age-related α-synuclein toxicity in a Caenorhabditis elegans model. Depletion of tdo-2 also suppresses toxicity of other heterologous aggregation-prone proteins, including amyloid-β and polyglutamine proteins, and endogenous metastable proteins that are sensors of normal protein homeostasis. This finding suggests that tdo-2 functions as a general regulator of protein homeostasis. Analysis of metabolite levels in C. elegans strains with mutations in enzymes that act downstream of tdo-2 indicates that this suppression of toxicity is independent of downstream metabolites in the kynurenine pathway. Depletion of tdo-2 increases tryptophan levels, and feeding worms with extra l-tryptophan also suppresses toxicity, suggesting that tdo-2 regulates proteotoxicity through tryptophan. Depletion of tdo-2 extends lifespan in these worms. Together, these results implicate tdo-2 as a metabolic switch of age-related protein homeostasis and lifespan. With TDO and Indoleamine 2,3-dioxygenase as evolutionarily conserved human orthologs of TDO-2, intervening with tryptophan metabolism may offer avenues to reducing proteotoxicity in aging and age-related diseases.     

Association of methylenetetrahydrofolate reductase polymorphisms with susceptibility to Alzheimer's disease

Background

Genetic risk factors play an important role in the pathogenesis of Alzheimer's disease (AD). In this case-control study, we examined the C677T and A1298C polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene and their correlation with this pathology.

Objective

To verify the association between MTHFR C677T and A1298C polymorphisms and Alzheimer's disease.

Method

This work was conducted as a case–control study. Cases consisted of thirty-eight patients and 100 individuals without dementia constituted the control group. Genotyping of MTHFR polymorphisms was performed on patients and controls.

Result

Genetic analyses did not indicate a significant association between the MTHFR C677T mutation and AD (C/T: 63.15% versus 39%, p = 0.087). However, the genotype prevalence of the missense variant MTHFR A1298C was significantly different between patients and controls (A/C: 55% versus 7%, p < 10⁻³). Our data suggest an association between the MTHFR A1298C mutation and AD; however, the MTHFR C677T mutation did not contribute to susceptibility for AD.

Conclusion

The MTHFR A1298C polymorphism is a possible risk factor for Alzheimer's disease.     

β‐amyloid and ATP‐induced diffusional trapping of astrocyte and neuronal metabotropic glutamate type‐5 receptors

β‐Amyloid (Aβ) oligomers initiate synaptotoxicity following their interaction with the plasma membrane. Several proteins including metabotropic glutamate type 5 receptors (mGluR5s) contribute to this process. We observed an overexpression of mGluR5s in reactive astrocytes surrounding Aβ plaques in brain sections from an Alzheimer's disease mouse model. In a simplified cell culture system, using immunocytochemistry and single molecule imaging, we demonstrated a rapid binding of Aβ oligomers on the plasma membrane of astrocytes. The resulting aggregates of Aβ oligomers led to the diffusional trapping and clustering of mGluR5s. Further, Aβ oligomers induced an increase in ATP release following activation of astroglial mGluR5s by its agonist. ATP slowed mGluR5s diffusion in astrocytes as well as in neurons co‐cultured with astrocytes. This effect, which is purinergic receptor‐dependent, was not observed in pure neuronal cultures. Thus, Aβ oligomer‐ and mGluR5‐dependent ATP release by astrocytes may contribute to the overall deleterious effect of mGluR5s in Alzheimer's disease. GLIA 2013;61:1673–1686     

Biodegradable and plasma‐treated electrospun scaffolds coated with recombinant Olfactomedin‐like 3 for accelerating wound healing and tissue regeneration

Three‐dimensional biomimetic scaffolds resembling the native extracellular matrix (ECM) are widely used in tissue engineering, however they often lack optimal bioactive cues needed for acceleration of cell proliferation, neovascularization, and tissue regeneration. In this study, the use of the ECM‐related protein Olfactomedin‐like 3 (Olfml3) demonstrates the importance and feasibility of fabricating efficient bioactive scaffolds without in vitro cell seeding prior to in vivo implantation. First, in vivo proangiogenic properties of Olfml3 were shown in a murine wound healing model by accelerated wound closure and a 1.4‐fold increase in wound vascularity. Second, subcutaneous implantation of tubular scaffolds coated with recombinant Olfml3 resulted in enhanced cell in‐growth and neovascularization compared with control scaffolds. Together, our data indicates the potential of Olfml3 to accelerate neovascularization during tissue regeneration by promoting endothelial cell proliferation and migration. This study provides a promising concept for the reconstruction of damaged tissue using affordable and effective bioactive scaffolds.