The age-related changes of trunk responses to Achilles tendon vibration

The contribution of different sensory modalities to balance control is modified by age. Postural responses to Achilles tendon vibration were investigated in order to understand the influence of age on proprioceptive input from lower legs in human stance. Postural responses to bilateral vibrations of Achilles tendon with 10 s duration were recorded at three frequencies (40, 60 and 80 Hz) in 9 healthy young (range, 24–27 years) and in 9 healthy older adults (59–70 years). Subjects were instructed to keep standing on firm surface with eyes closed. They performed three trials in each of three vibration frequencies. Postural responses were characterized by displacement of the centre of foot pressure (CoP) and by kinematics of body segments in the anterior–posterior direction. Bilateral vibrations of Achilles tendon induced backward body lean increasing with frequency of vibration and with age. The leg angle response to vibration was found similar in both groups of subjects. Slight trunk tilts from vertical position were induced by vibration in young subjects while in older subjects the trunk tilted backward together with the whole body. This observation was supported also by the minimal change of hip angle in older subjects contrary to increased hip activity in young subjects. The findings showed that the trunk and hip angle responses to proprioceptive stimulation might be a good indicator of age-related destabilization in balance control.     

Expression and localization of augmenter of liver regeneration in human muscle tissue

Mitochondrial DNA (mt-DNA) disorders and abnormal regulation of nuclear-derived proteins devoted to the cross-talk between the two cellular genomes have recently interested researchers in the field of neuromuscular diseases. We have identified, isolated and sequenced a new gene, augmenter of liver regeneration (ALR) that stimulates in vivo hepatocyte proliferation and up-regulates mt-DNA expression and ATP production. ALR protein (Alrp) is mainly located, in rat, in the mitochondrial inter-membrane space and its mRNA is particularly abundant in brain, muscle, testis and liver, tissues whose activity is mostly dependent on mitochondrial metabolism. Studies on rat Alrp sequence revealed the presence of homologous amino-acid sections into proteins derived from mouse, human, Drosophyla, plants and even DNA viruses. In this article, we evaluated ALR expression in normal human muscular tissues, both as protein and as mRNA. The data, obtained by molecular biology, immunohistochemistry and electron microscopy, demonstrated that: (i) Alrp and ALR mRNA are present in human muscular tissue; (ii) Alrp is particularly expressed in muscular fibres rich in mitochondria; (iii) Alrp is localized in the mitochondrial inter-membrane space or associated to mitochondrial cristae; and (iv) in subjects younger then 35 years of age, ALR mRNA expression is different between male and female subjects. In conclusion, the present data set Alrp, as a factor associated with mitochondria also in human tissue, call for future studies aimed at establishing Alrp as an important factor involved in the molecular events that trigger neuromuscular diseases.     

Cutaneous distribution of plasmacytoid dendritic cells in lupus erythematosus. Selective tropism at the site of epithelial apoptotic damage

Recent evidences suggest a significant role of Plasmacytoid dendritic cells (PDC) role in the pathogenesis of lupus erythematosus (LE) via production of type I IFN. Taking advantage on the availability of multiple reagents (CD123, BDCA2, and CD2ap) specifically recognizing PDC on fixed tissues, we investigated the occurrence of PDC in a cohort of 74 LE patients. The large majority of LE biopsies (67/74; 90.5%) showed cutaneous infiltration of PDC. PDC were more frequently observed (96.4 vs 72.2) and numerous in cutaneous LE compared to systemic LE (SLE) and correlated with the density of the inflammatory infiltrate (r=0.40; p<0.001). PDC reduction in SLE might be related to a broader tissue distribution of this cellular population, as indicated by their occurrence in kidneys in 11 out of 24 (45.8%) cases studied. The distribution of cutaneous PDC showed two distinct patterns. More commonly, PDC were observed within perivascular inflammatory nodules in the dermis, associated with CD208+ mature DC and T-bet+ cells [D-PDC]. A second component was observed along the dermal-epithelial junction [J-PDC], in association with cytotoxic T-cells in areas of severe epithelial damage. Notably, chemerin reactivity was observed in 64% of LE biopsies on endothelial cells and in the granular layer keratinocytes. Cutaneous PDC in LE strongly produced type I IFN, as indicated by the diffuse MxA expression, and the cytotoxic molecule granzyme B.This study confirms cutaneous PDC infiltration as hallmark of LE. The topographical segregation in D-PDC and J-PDC suggests a novel view of the role of these cells in skin autoimmunity.     

Use of calcium supplements and the risk of coronary heart disease in 52–62-year-old women: The Kuopio Osteoporosis Risk Factor and Prevention Study

Background

To analyse prospectively the effect of calcium or calcium + D supplementation on coronary heart disease (CHD) in 52–62-year-old women.

Methods and results

10,555 52–62-year-old women from the population-based Kuopio Osteoporosis Risk Factor and Prevention Study (OSTPRE) who did not have CHD at baseline were followed for nearly 7 years in 1994–2001. Information about use of calcium supplements and health events was obtained from two repeated questionnaires in 1989 and 1994. Information about causes of death during the follow-up was obtained from the Statistics Finland. Information about CHD and other disease morbidity before and during the follow-up was obtained from the Registry of Specially Refunded Drugs of the Finnish Social Insurance Institution (SII). Cox's proportional-hazards models were used to estimate the risk of CHD morbidity related to the use of calcium supplements. At baseline, 2723 women reported current use of calcium or calcium + D supplementation. During the follow-up, CHD was diagnosed in 513 women. Compared to non-users of calcium/calcium + D supplements, the multivariate adjusted hazard ratio (HR) of CHD was 1.24 (95% CI 1.02–1.52) in women who used these supplements. The multivariate adjusted HR for CHD morbidity in postmenopausal women who used calcium/calcium + D supplements was 1.26 (95% CI 1.01–1.57).

Conclusions

Calcium or calcium + D supplementation appears to increase the risk of CHD among women before old age.     

Immunohistochemical identification of MMP-2 and MMP-9 in human dentin: correlative FEI-SEM/TEM analysis

Matrix metalloproteinases (MMPs) are a family of peptidases trapped within mineralized dentin matrix and involved with degradation of the extracellular matrix components in hybrid layers and caries. Despite their identification through indirect evidences and biochemical assays, MMP-2 and -9 have not been localized within the human dentin extracellular organic matrix. Thus, this study aimed to assess the localization and distribution of MMP-2 and -9 in human dentin organic matrix by employing a correlative field emission in-lens-scanning electron microscopy (FEI-SEM) and transmission electron microscopy (TEM) immunohistochemical approach. Dentin specimens were submitted either to a preembedding or to a postembedding immunolabeling technique using primary monoclonal antibodies anti-MMP-2 and anti-MMP-9 and exposed to a secondary antibody conjugated with gold nanoparticles. MMP-2 and -9 labelings were identified in the demineralized dentin matrix as highly electron-dense gold particles dispersed on the collagen fibrils. Correlative FEI-SEM/TEM observations confirmed that MMP-2 and MMP-9 are endogenous components of the human dentin organic matrix and revealed the three-dimensional relationship between these proteinases and the collagen fibrils, showing that both antibodies yielded a similar labeling pattern. In conclusion, the results of the study contribute to reveal distinct distribution pattern of gelatinases and support the hypothesis that these enzymes are intrinsic constituents of the dentin organic matrix after decalcification.     

Immunolocalization of G‐Protein Alpha Subunits in the Olfactory System of the Cartilaginous Fish Scyliorhinus Canicula

In the olfactory and vomeronasal systems of vertebrates, the morphology of the receptor neurons, the receptor gene family they express, the G‐protein coupled with the receptor (in particular the G‐protein alpha subunit), and their projection to the olfactory bulb are correlated. Much information about this complicated system have been collected in different groups, but nothing is known about Chondrichthyes. In this work, the presence and distribution of immunoreactivity for different types of G‐protein alpha subunit (Gα_o, Gα_q and Gα_s/olf) were investigated in the olfactory mucosa and olfactory bulb of the shark Scyliorhinus canicula. Only Gα_o‐like immunoreactivity was detected in the olfactory mucosa and bulb, both in tissues and homogenates. Its distribution was partially similar to that found in other vertebrates: it was localized in the microvillous receptor neurons, in numerous axon bundles of the fila olfactoria, in the stratum nervosum and in the most of glomeruli in the stratum glomerulosum. No immunoreactivity was instead observed in the crypt neurons, the second type of olfactory neurons present in cartilaginous fish. The projections of crypt neurons to olfactory bulb probably correspond to the few ventrally‐located glomeruli which were negative to the antiserum against Gα_o. These data suggest, in S. canicula, different olfactory neuron types send projections to the olfactory bulb with a segregated distribution, as observed in other vertebrates. Anat Rec, 2009. © 2009 Wiley‐Liss, Inc.     

IFN‐α‐mediated increase in cytolytic activity of maturing NK cell upon exposure to HSV‐infected myelomonocytes

Impaired control of chronic pathogen replication may be associated to alterations of NK‐cell function. Whether mechanisms underlying this dysfunction involve perturbations of differentiating NK cells is still unknown. We studied an “in vitro” model of differentiation from CD34⁺Lin^? precursors growing only myelomonocytes and maturing NK cells and where myelomonocytes could be suitably infected with HSV, HIV, or vaccinia. Cultures were evaluated by cytofluorometry and cytotoxicity assays for perturbations in differentiating NK cells. Increased expression of natural cytotoxicity receptors on maturing NK cells with increased cytolytic activity was observed with HSV‐1 infection, and with vaccinia while no modulation of NK‐cell phenotype nor cytotoxic activity were evident with an ssRNA lentivirus (HIV‐1). In the presence of constant IL‐12 and IL‐15 concentrations, the observed effect did not require cell contact, involved IFN‐αand was not reproduced by the addition of TLR9 agonist, nor blocked by TLR9 antagonists. Virus replication at sites of NK‐cell precursor development may have different outcomes depending on the interaction between invading viruses and maturing NK cells. Thus, NK‐cell precursors may be involved in the immune response to dsDNA viruses and possibly contribute to efficient control of virus infection.     

Are drawing perseverations part of the neglect syndrome?

Unilateral neglect patients typically omit to cancel contralesional targets. Moreover, they can repeatedly cancel ipsilesional stimuli exhibiting what is termed ‘perseverative behavior’. Two alternative accounts of this behavior have been proposed. According to one of them, it is considered as integral to neglect and due either to a perceptual (allochiria), or a premotor (directional hypokinesia) pathological mechanism leading to the ipsilesional displacement of contralesional responses. According to the other one, perseverations are interpreted as the consequence of motor-control-disinhibition co-occurring with, although independent of, spatial neglect. We compared some crucial predictions of these two hypotheses on a group of 10 right-brain-damaged patients, eight with neglect and two without neglect, showing a perseverative behavior in both conventional and experimental cancellation tasks. In our experiment, the spatial location and the numerosity of targets were manipulated to obtain different degrees of horizontal alignment between targets on the left and on the right of the central vertical axis of the sheet. We found that ipsilesional perseverations were not influenced by left neglected targets and were not correlated to neglect severity. Additionally, perseverative errors were associated with right basal ganglia lesions rather than with presence of neglect. These findings support the view that two different pathological mechanisms might be involved in left spatial neglect and ipsilesional perseverative behavior.     

Efficacy of traditional and biologic agents in different clinical phenotypes of adult‐onset Still's disease

Objective

To evaluate the efficacy of antiinflammatory agents, steroids, immunosuppressants, and biologic agents in patients with adult‐onset Still's disease (AOSD) who have either chronic articular disease or nonchronic disease.

Methods

Forty‐five patients with AOSD were seen and followed up for at least 2 years at our institution, from 1991 to 2008. The majority of patients were treated with several therapeutic regimens; a total of 152 efficacy trials were administered. Data regarding the type of medication, the dosage used, and the outcome of these trials were collected and analyzed.

Results

Our data showed that the efficacy of monotherapy with a nonsteroidal antiinflammatory drug was very low (16%) and confirmed good efficacy of steroid therapy (63%), particularly in patients without chronic articular disease (78%). Patients whose disease did not respond to steroid therapy at the time of disease onset were at risk of the subsequent development of chronic arthritis. Disease‐modifying antirheumatic drug (DMARD) monotherapy was successful in controlling steroid‐resistant or steroid‐dependent disease in 60% of patients. Methotrexate and cyclosporine showed the best response rates. The combination of high‐dose steroids and cyclosporine was administered to successfully control some acute life‐threatening complications. Only 6 patients had disease that was both steroid resistant and DMARD resistant. Treatment with biologic agents eventually led to satisfactory control of disease manifestations in 5 (83%) of these 6 patients.

Conclusion

Steroids were less effective in patients with chronic articular disease than in those with nonchronic disease. The administration of DMARDs early after disease onset could be beneficial in patients with steroid‐resistant disease who are at risk of the development of chronic articular disease. Biologic agents proved to be highly effective in both steroid‐resistant and DMARD‐resistant AOSD.