Oxidative tissue injury in multiple sclerosis is only partly reflected in experimental disease models

Recent data suggest that oxidative injury may play an important role in demyelination and neurodegeneration in multiple sclerosis (MS). We compared the extent of oxidative injury in MS lesions with that in experimental models driven by different inflammatory mechanisms. It was only in a model of coronavirus-induced demyelinating encephalomyelitis that we detected an accumulation of oxidised phospholipids, which was comparable in extent to that in MS. In both, MS and coronavirus-induced encephalomyelitis, this was associated with massive microglial and macrophage activation, accompanied by the expression of the NADPH oxidase subunit p22phox but only sparse expression of inducible nitric oxide synthase (iNOS). Acute and chronic CD4⁺ T cell-mediated experimental autoimmune encephalomyelitis lesions showed transient expression of p22phox and iNOS associated with inflammation. Macrophages in chronic lesions of antibody-mediated demyelinating encephalomyelitis showed lysosomal activity but very little p22phox or iNOS expressions. Active inflammatory demyelinating lesions induced by CD8⁺ T cells or by innate immunity showed macrophage and microglial activation together with the expression of p22phox, but low or absent iNOS reactivity. We corroborated the differences between acute CD4⁺ T cell-mediated experimental autoimmune encephalomyelitis and acute MS lesions via gene expression studies. Furthermore, age-dependent iron accumulation and lesion-associated iron liberation, as occurring in the human brain, were only minor in rodent brains. Our study shows that oxidative injury and its triggering mechanisms diverge in different models of rodent central nervous system inflammation. The amplification of oxidative injury, which has been suggested in MS, is only reflected to a limited degree in the studied rodent models.     

Maternal corticosterone is transferred into the egg yolk

Hormones deposited in the avian egg are considered in many studies to influence or to adjust offspring phenotype to prevailing conditions in an adaptive way. Several studies demonstrated an effect of corticosterone, the main glucocorticoid in birds, injected into the egg on the developing chick, but the injection of steroids in the egg is far from mimicking the natural distribution of the hormone in the egg. Other studies applied a stressor or corticosterone to the mother. However it is still debated whether an increase of circulating corticosterone in the mother translates into higher concentrations of corticosterone in the egg. Therefore, we investigated in captive barn owls Tyto alba whether circulating corticosterone in egg-laying females elevated within a physiological range, resulted in the deposition of corticosterone in eggs. We found that an increase in circulating corticosterone in the mother within the naturally occurring range translated into elevated concentrations of corticosterone in the yolk of subsequently laid eggs, indicating a specific time frame and yolk layer of corticosterone deposition. We conclude that increasing maternal plasma corticosterone within a naturally occurring range is an efficient tool to increase corticosterone concentration in the egg and to manipulate conditions for the developing embryo.     

Regulatory element copy number differences shape primate expression profiles

Gene expression differences are shaped by selective pressures and contribute to phenotypic differences between species. We identified 964 copy number differences (CNDs) of conserved sequences across three primate species and examined their potential effects on gene expression profiles. Samples with copy number different genes had significantly different expression than samples with neutral copy number. Genes encoding regulatory molecules differed in copy number and were associated with significant expression differences. Additionally, we identified 127 CNDs that were processed pseudogenes and some of which were expressed. Furthermore, there were copy number-different regulatory regions such as ultraconserved elements and long intergenic noncoding RNAs with the potential to affect expression. We postulate that CNDs of these conserved sequences fine-tune developmental pathways by altering the levels of RNA.     

Etiology of Anemia Among Infants, School-Aged Children, and Young Non-Pregnant Women in Different Settings of South-Central Cote d'Ivoire

Anemia affects one-quarter of the world''s population, but its etiology remains poorly understood. We determined the prevalence of anemia and studied underlying risk factors in infants (6–23 months), young school-aged children (6–8 years), and young non-pregnant women (15–25 years) in south-central Côte d''Ivoire. Blood, stool, and urine samples were subjected to standardized, quality-controlled methods. We found high prevalence of anemia, malaria, inflammation, and deficiencies of iron, riboflavin, and vitamin A but low prevalence and intensities of soil-transmitted helminth and schistosome infections. Multivariate regression analysis revealed significant associations between anemia and Plasmodium falciparum for infants, inflammation for school-aged children, and cellular iron deficiency for both school-aged children and non-pregnant women. Women with riboflavin deficiency had significantly lower odds of anemia. Our findings call for interventions to protect infants from malaria, improved intake of dietary iron, better access to health care, and health education.     

Influence of the crown-to-implant length ratio on the clinical performance of implants supporting single crown restorations: a cross-sectional retrospective 5-year investigation

Purpose: The aim of this study was to investigate the influence of the crown‐to‐implant length ratio (c/i ratio) on the implant survival, changes of the marginal bone level (MBL) and the occurrence of biological and technical complications. Material and methods: This cross‐sectional retrospective study included all patients with implants in the posterior segments supporting single crown restorations with a minimum follow‐up of 5 years. All patients were questioned and examined clinically and radiographically. The technical and biological c/i ratio and the MBL were measured on digitized periapical radiographs. The following outcome parameters in relation to the c/i ratio and the co‐factors were statistically analyzed: implant survival rate, MBL, occurrence of technical and biological complications. For statistical analysis, regression, correlation and survival analyses were applied (P<0.05). Results: Seventy patients (mean age of 50.7 years [range 19.8–76.6 years]) with a total of 100 implants (24 Straumann type, 76 Brånemark type) were included in this study. The mean follow‐up period was 6.2 years (range 4.73–11.7 years). Six implants failed during the follow‐up period, yielding a cumulative survival rate of 95.8% at 5 years in function. The mean technical c/i ratio was 1.04 (±0.26, range 0.59–2.01). The mean biological c/i ratio was 1.48 (±0.42, range 0.82–3.24). No statistically significant influence of the technical and biological c/i ratio was found on the implant survival, MBL and occurrence of technical and biological complications. When adjusted for the biological c/i ratio, smoking was the only co‐factor significantly associated with implant failure and biological complications. Conclusion: In the present study, the c/i ratio did not influence the clinical performance of implants supporting single crown restorations in the posterior segments of the jaw within the range tested. To cite this article:
Schneider D, Witt L, Hämmerle CHF. Influence of the crown‐to‐implant length ratio on the clinical performance of implants supporting single crown restorations: a cross‐sectional retrospective 5‐year investigation.
Clin. Oral Impl. Res. 23 , 2012; 169–174.
doi: 10.1111/j.1600‐0501.2011.02230.x     

Mast cells play a protumorigenic role in primary cutaneous lymphoma

Primary cutaneous lymphomas (PCLs) are clonal T- or B-cell neoplasms, which originate in the skin. In recent years, mast cells were described as regulators of the tumor microenvironment in different human malignancies. Here, we investigated the role of mast cells in the tumor microenvironment of PCL. We found significantly increased numbers of mast cells in skin biopsies from patients with cutaneous T-cell lymphoma (CTCL) and cutaneous B-cell lymphoma (CBCL). Mast cell infiltration was particularly prominent in the periphery, at lymphoma rims. Interestingly, CTCL and CBCL patients with a progressive course showed higher mast cell counts than stable patients, and mast cell numbers in different stages of CTCL correlated positively with disease progression. In addition, mast cell numbers positively correlated with microvessel density. Incubating primary CTCL cells with mast cell supernatant, we observed enhanced proliferation and production of cytokines. In line with our in vitro experiments, in a mouse model of cutaneous lymphoma, tumor growth in mast cell-deficient transgenic mice was significantly decreased. Taken together, these experiments show that mast cells play a protumorigenic role in CTCL and CBCL. Our data provide a rationale for exploiting tumor-associated mast cells as a prognostic marker and therapeutic target in PCL.     

A 1-Year Randomized Controlled Study of Everolimus Versus Mycophenolate Mofetil With Reduced-Dose Cyclosporine in Maintenance Heart Transplant Recipients

Background

The aim of this study was to demonstrate noninferiority of everolimus with reduced cyclosporine (CsA) vs mycophenolate mofetil (MMF) with reduced CsA in improving renal function.

Methods

In this 1-year randomized, open-label, noninferiority study in maintenance heart transplant recipients with impaired renal function 70 patients received everolimus (n = 36) or MMF (n = 34) in combination with reduced CsA. The planned sample size was not reached as the study was prematurely discontinued due to slow recruitment.

Results

Noninferiority of the everolimus regimen could not be shown: In the total population MMF seemed to be favorable on renal function assessed by serum creatinine and filtration rates, but not in the subset of patients who reached the intended reduced CsA level. Incidence rates of rejection episodes were significantly higher under MMF at month 6 (P = .0332).

Conclusions

Overall, the results of this trial using reduced CsA in combination with either everolimus or MMF show that there is evidence to reduce the CsA level when everolimus is given concomitantly and that the benefit of MMF with reduced CsA levels is limited due to insufficient immunosuppression.