Involvement of chromosomes 12 and 14 in the cutaneous stage of mycosis fungoides: Cytogenetic evidence for a multistep pathogenesis of the disease

Cytogenetic studies were performed on the cells of bone marrow, peripheral blood, and skin tumor biopsies from a patient with mycosis fungoides at an early stage. Chromosome abnormalities were detected in 100% of the cells harvested from the cutaneous specimen, whereas the cells of the bone marrow and blood were karyotypically normal. Three related clones, showing increasing cytogenetic complexity, were found. Chromosome #12 was abnormal in all metaphases, and an abnormal 14q chromosome was present in a minority of cells belonging to the most complex emerging subclone. These data, along with the finding of important signs of chromosome imbalance, suggest a polyphasic evolution of this chronic T lymphoproliferative disease.     

A bone substitute composed of polymethylmethacrylate and alpha-tricalcium phosphate: results in terms of osteoblast function and bone tissue formation

The biological properties of a composite polymeric matrix (PMMA + alpha-TCP) made of polymethylmethacrylate (PMMA) and alfa-tricalciumphosphate (alpha-TCP) was tested by means of in vitro and in vivo investigations. PMMA was used as a comparative material. Osteoblast cultures (MG 63) demonstrated that PMMA + alpha-TCP significantly and positively affected osteoblast viability, synthetic activity and interleukin-6 level as compared to PMMA. At 12 weeks, the PMMA + alpha-TCP implants in rabbit bone successfully osteointegrated in trabecular and cortical tissue (affinity index: 57.14+/-8.84% and 68.31+/-6.18%, respectively). The newly formed bone after tetracycline labelling was histologically observed inside PMMA + alpha-TCP porosity. The microhardness test at the bone-PMMA + alpha-TCP interface showed a significantly higher rate of newly formed bone mineralization compared with PMMA (+83.5% and +58.5%, respectively), but differences still existed between newly formed and pre-existing normal bone. It is herein hypothesized that the present positive results may be ascribed to the porous macroarchitecture of PMMA + alpha-TCP and the presence of the bioactive ceramic material that could have a synergic effect and be responsible for the improvement of (a) the material colonization by bone cells, (b) osteoblast activity, (c) osteoinduction and osteoconduction processes, (d) bone remodelling.     

Cartilage engineering from ovine umbilical cord blood mesenchymal progenitor cells

We aimed to determine whether three-dimensional (3D) cartilage could be engineered from umbilical cord blood (CB) cells and compare it with both engineered fetal cartilage and native tissue. Ovine mesenchymal progenitor cells were isolated from CB samples (n=4) harvested at 80-120 days of gestation by low-density fractionation, expanded, and seeded onto polyglycolic acid scaffolds. Constructs (n=28) were maintained in a rotating bioreactor with serum-free medium supplemented with transforming growth factor-beta1 for 4-12 weeks. Similar constructs seeded with fetal chondrocytes (n=13) were cultured in parallel for 8 weeks. All specimens were analyzed and compared with native fetal cartilage samples (n=10). Statistical analysis was by analysis of variance and Student's t-test (p<.01). At 12 weeks, CB constructs exhibited chondrogenic differentiation by both standard and matrix-specific staining. In the CB constructs, there was a significant time-dependent increase in extracellular matrix levels of glycosaminoglycans (GAGs) and type-II collagen (C-II) but not of elastin (EL). Fetal chondrocyte and CB constructs had similar GAG and C-II contents, but CB constructs had less EL. Compared with both hyaline and elastic native fetal cartilage, C-II and EL levels were, respectively, similar and lower in the CB constructs, which had correspondingly lower and similar GAG levels than native hyaline and elastic fetal cartilage. We conclude that CB mesenchymal progenitor cells can be successfully used for the engineering of 3D cartilaginous tissue in vitro, displaying select histological and functional properties of both native and engineered fetal cartilage. Cartilage engineered from CB may prove useful for the treatment of select congenital anomalies.     

Experimental muscle pain changes motor control strategies in dynamic contractions

This study investigated the effect of muscle pain on muscle activation strategies during dynamic exercises. Ten healthy volunteers performed cyclic elbow flexion/extension movements at maximum speed for 2 min after injection of (1) hypertonic (painful) saline in the biceps brachii, (2) hypertonic saline in both biceps brachii and triceps brachii, and (3) isotonic (nonpainful) saline in the biceps brachii muscle. Surface electromyographic (EMG) signals were collected from the upper trapezius, biceps brachii, triceps brachii, and brachioradialis muscles (to estimate EMG amplitude) and with an electrode arrays from biceps brachii (to estimate muscle fiber conduction velocity [CV]). In all conditions, the acceleration of the movement decreased throughout the exercise, and kinematic parameters were not altered by pain. With respect to the control condition, pain induced a decrease of the biceps brachii (mean ± SE, –23±4%) and brachioradialis (–10±0.4%) integrated EMG (IEMG) in the beginning of the exercise, and an increase (45±3.5%) of the upper trapezius IEMG at all time points during the exercise. The biceps brachii IEMG decreased over time during the nonpainful exercises (–11±0.6%) while it remained constant in the painful condition. Biceps brachii CV decreased during painful conditions (–12.8±2.2%) while it remained constant during the nonpainful condition. In conclusion, muscle pain changes the motor control strategy to sustain the required dynamic task both in the relative contribution between synergistic muscles and in the motor unit activation within the painful muscle. Such a changed motor strategy may be highly relevant in models of occupational musculoskeletal pain conditions.     

3q−, 3q+ anomaly in malignant proliferations in humans

Anomalies of both No. 3 chromosomes, of the t(3q?; 3q+) type can be observed in human malignancy as reported previously. It is our experience that this anomaly is found predominantly in myeloproliferative disorders, as a rather rare event, though occurring more frequently than similar exchanges between other homologous chromosomes. Previous claims about a relationship between this anomaly and thrombocytosis could not be confirmed, but the features found in a few patients indicate that further research should be undertaken to clarify this point.     

The surface measurement of aortic atherosclerosis: critical survey and comparison with histologic findings

Both the reproducibility of the surface measurements of aortic atherosclerosis and the agreement between gross inspective and histologic changes were evaluated. Aortas from male broad breasted white turkeys were chosen because of the high incidence of spontaneous and typical atherosclerotic lesions in this animal strain. Ten male turkeys were killed at 33 weeks of age. The aortas were removed including the iliac bifurcation and stained with Sudan III. Each aorta was processed blindly by four pathologists and a computerized planimeter to determine normal areas, sudanophilic areas and areas covered by plaques. The analysis of variance showed significant differences among the four pathologists' measurements of sudanophilic areas (P less than 0.01) and areas covered by plaques (P less than 0.001). The coefficients of variation among the four determinations made by one pathologist on the same aorta were 3.6% for total aortic area; 10.08% for sudanophilic area; 47.6% for the area covered by plaques. On each aorta histology was performed at the level where all the four pathologists recorded the same findings at inspection, namely a normal area, a sudanophilic area, and an area covered by plaques. Important discrepancies occurred between findings at inspection and those of histologic examination: the ten areas classified as "normal" by all the four pathologists at inspection were shown at histologic examination to be normal in only two cases. In one case a musculo-elastic layer and in seven cases a fibro-elastic layer were found. The ten areas classified as "sudanophilic" by all the observers showed a fibro-elastic layer in five cases, a musculo-elastic layer in two cases and normal findings in three cases. The ten areas classified as "covered by plaques" displayed a typical atherosclerotic plaque in all cases but one. In conclusion, our data indicate that the reproducibility of gross inspective methods is low. Important discrepancies exist between findings at inspection and histologic examinations. The relevance of these findings remains to be established as far as the assessment of human atherosclerosis is concerned.     

Role of Cachexia and Fragility in the Patient Candidate for Cardiac Surgery

Frailty is the major expression of accelerated aging and describes a decreased resistance to stressors, and consequently an increased vulnerability to additional diseases in elderly people. The vascular aging related to frail phenotype reflects the high susceptibility for cardiovascular diseases and negative postoperative outcomes after cardiac surgery. Sarcopenia can be considered a biological substrate of physical frailty. Malnutrition and physical inactivity play a key role in the pathogenesis of sarcopenia. We searched on Medline (PubMed) and Scopus for relevant literature published over the last 10 years and analyzed the strong correlation between frailty, sarcopenia and cardiovascular diseases in elderly patient. In our opinion, a right food intake and moderate intensity resistance exercise are mandatory in order to better prepare patients undergoing cardiac operation.     

Formyl Peptide Receptor (FPR)1 Modulation by Resveratrol in an LPS-Induced Neuroinflammatory Animal Model

Among therapeutic approaches that have been investigated, targeting of receptors implicated in managing neuroinflammation has been described. One such family of receptors comprises the formyl peptide receptors (FPRs) whose ligands could play a role in host defense. The murine FPR gene family includes at least six members while in humans there are only three. The two most important members are the Fpr1 and Fpr2. Fpr1encodes murine FPR1, which is considered the murine orthologue of human FPR. Resveratrol, a non-flavonoid polyphenol rich in red wine and grapes, apart from its beneficial health effects and anti-inflammatory properties, has been reported to reduce neuroinflammation in different neurodegenerative disease models. Resveratrol anti-inflammatory responses involve the activation of the protein deacetylase sirtuin 1 (SIRT1) gene. In this work we have investigated in an LPS-based murine model of neuroinflammation the role of FPR1, examining not only if this receptor undergoes a reduction of its expression during neuroinflammation, but also whether treatment with resveratrol was able to modulate its expression leading to an amelioration of neuroinflammatory picture in a murine model of neuroinflammation. Results of this work showed that FPR1 together with SIRT1 resulted upregulated by resveratrol treatment and that this increase is associated with an amelioration of the neuroinflammatory picture, as demonstrated by the induction of IL-10 and IL1-RA expression and the downregulation of proinflammatory mediators, such as TNF-α and IL-1β. The expression and the modulation of FPR1 by resveratrol may be evaluated in order to propose a novel anti-inflammatory and pro-resolving therapeutic approach for the reduction of the detrimental effects associated with neuro-inflammation based neurodegenerative diseases and also as a promising strategy to promote human health by a diet rich in antioxidative bioactive compounds.     

Vascular Effects of the Polyphenolic Nutraceutical Supplement Taurisolo®: Focus on the Protection of the Endothelial Function

Preservation of vascular endothelium integrity and functionality represents an unmet medical need. Indeed, endothelial dysfunction leads to decreased nitric oxide biosynthesis, which is prodromic of hypertension and hypercoagulability. In this panorama, the nutraceutical supplement Taurisolo^®, a polyphenolic extract from Aglianico cultivar grape, rich in catechin and procyanidins, was evaluated as a vasoprotective, vasorelaxing, anti-hypertensive and anti-coagulant agent in: cell lines, isolated vessels, in vivo models of chronic hypertension and hypercoagulability, and in clinical tests of endothelial reactivity. Taurisolo^® demonstrated to fully protect vascular cell viability from oxidative stimulus at 100 µg/mL and evoke vasorelaxing effects (Emax = 80.6% ± 1.9 and pEC50 = 1.19 ± 0.03) by activation of the Sirtuins-AMPK-pathway. Moreover, Taurisolo^®, chronically administered at 20 mg/Kg/die in in vivo experiments, inhibited the onset of cardiac hypertrophy (heart weight/rat weight = 3.96 ± 0.09 vs. 4.30 ± 0.03), hypercoagulability (decrease of fibrinogen vs. control: p < 0.01) and hypertension (mean of Psys: 200 ± 2 vs. control 234 ± 2 mmHg) and improved endothelial function (Emax = 88.9% ± 1.5 vs. control 59.6% ± 3.6; flow-mediated dilation in healthy volunteers after 400 mg twice daily for 8 weeks vs. baseline: p = 0.019). In conclusion, Taurisolo^® preserves the vascular function against ox-inflamm-ageing process and the consequent cardiovascular accidents.