The Importance of Perioperative Administration of an Anti-Hyperalgesic Drug in Burn Wounds

The importance of perioperative administration of an anti-hyperalgesic drug in burn wounds

Bone microarchitecture as an important determinant of bone strength.

Structure and microarchitecture are determinant aspects of bone strength and essential elements for the assessment of bone mechanical properties. The main structural determinants of bone mechanical strength include width and porosity in the cortical bone; shape, width, connectivity, and anisotropy in the trabecular bone. There are several methods to assess bone architecture, particularly at the trabecular level. Two different approaches can be identified. The first is based on the use of optical microscopy and on the principles of quantitative histology, which evaluate microarchitecture two-dimensionally. The second applies the most modern diagnostic techniques, employing computed tomography and magnetic resonance to obtain and analyze three-dimensional images. From a clinical point of view, microarchitecture is an interesting aspect to study and define specific patterns, such as glucocorticoid-induced osteoporosis, or to evaluate bone alterations in transplanted patients. Microarchitecture seems to be a determinant of bone fragility independent of bone density. Moreover, bone microarchitecture seems to be important to understand the mechanisms of bone fragility as well as the action of the drugs used to prevent osteoporotic fractures. Several in vivo studies (on animals and humans) showed important findings on the effects of different treatments on microarchitecture. Bisphosphonates and parathyroid hormone seemed to preserve or even improve microarchitecture. These observations can provide an additional interpretation for the anti-fracture effect of drugs from a structural viewpoint. The challenge for the future will be to evaluate bone quality in vivo with the same or better resolution and accuracy than the invasive methods in use today

Cambiamento climatico, inquinamento atmosferico e aumento delle allergie respiratorie: solo una coincidenza o qualcosa di più? [Climate change, air pollution, and increase of respiratory allergies: just a coincidence or something more?].

It is well known that the prevalence of respiratory allergies has increased over time. At the same time, climate change has become part of our everyday life. The resulting question is whether this 'allergic epidemic' is linked to this aspect. It is assumed that the causes of the increase of respiratory allergies are mainly related to environmental factors and lifestyle: first, the improvement of social and health conditions and related hygiene hypothesis; secondly, lifestyle change and anthropogenic activities, which have caused an alteration in the balance normally existing between soil, water, and atmosphere, giving rise to the phenomena of climate change. In fact, it has been demonstrated that they can influence beginning, duration, and intensity of the pollen season, as well as the allergenicity of pollen. The consequence is both an increase in frequency and intensity of allergic symptomatology in subjects previously affected by allergy, and a promotion of the sensitization of the airways to allergens present in the atmosphere in predisposed subjects. Several intervention strategies aiming to mitigate climate change and reduce anthropogenic emissions and, consequently, respiratory allergies are possible and can be implemented on an individual and social level. It follows that the allergist cannot solve the problem of the progressive increase of respiratory allergies on his own. Anyway, his role can have both clinical and educational purposes with a special commitment to reduce health impact due to environmental risk factors. KEYWORDS: respiratory allergies; allergenic potential of pollen; climate change; pollution

BEL \u3b2\u2010Trefoil Reduces the Migration Ability of RUNX2 Expressing Melanoma Cells in Xenotransplanted Zebrafish

RUNX2, a master osteogenic transcript ion factor, is overexpressed in several cancer cells; in melanoma it promotes cells migration and invasion as well as neoangiogenesis. The annual mortality rates related to metastatic melanoma are high and novel agents are needed to improve melanoma patients\u2019 survival. It has been shown that lectins specifically target malignant cells since they present the Thomsen\u2013Friedenreich antigen. This disaccharide is hidden in normal cells, while it allows selective lectins binding in transformed cells. Recently, an edible lectin named BEL \u3b2-trefoil has been obtained from the wild mushroom Boletus edulis. Our previous study showed BEL \u3b2-trefoil effects on transcription factor RUNX2 downregulation as well as on the migration ability in melanoma cells treated in vitro. Therefore, to better understand the role of this lectin, we investigated the BEL \u3b2-trefoil effects in a zebrafish in vivo model, transplanted with human melanoma cells expressing RUNX2. Our data showed that BEL \u3b2-trefoil is able to spread in the tissues and to reduce the formation of metastases in melanoma xenotransplanted zebrafish. In conclusion, BEL \u3b2-trefoil can be considered an effective biomolecule to counteract melanoma disease

Microarray Analysis on Human Neuroblastoma Cells Exposed to Aluminum, β1–42-Amyloid or the β1–42-Amyloid Aluminum Complex

BACKGROUND: A typical pathological feature of Alzheimer's disease (AD) is the appearance in the brain of senile plaques made up of β-amyloid (Aβ) and neurofibrillary tangles. AD is also associated with an abnormal accumulation of some metal ions, and we have recently shown that one of these, aluminum (Al), plays a relevant role in affecting Aβ aggregation and neurotoxicity. METHODOLOGY: In this study, employing a microarray analysis of 35,129 genes, we investigated the effects induced by the exposure to the Aβ(1-42)-Al (Aβ-Al) complex on the gene expression profile of the neuronal-like cell line, SH-SY5Y. PRINCIPAL FINDINGS: The microarray assay indicated that, compared to Aβ or Al alone, exposure to Aβ-Al complex produced selective changes in gene expression. Some of the genes selectively over or underexpressed are directly related to AD. A further evaluation performed with Ingenuity Pathway analysis revealed that these genes are nodes of networks and pathways that are involved in the modulation of Ca(2+) homeostasis as well as in the regulation of glutamatergic transmission and synaptic plasticity. CONCLUSIONS AND SIGNIFICANCE: Aβ-Al appears to be largely involved in the molecular machinery that regulates neuronal as well as synaptic dysfunction and loss. Aβ-Al seems critical in modulating key AD-related pathways such as glutamatergic transmission, Ca(2+) homeostasis, oxidative stress, inflammation, and neuronal apoptosis

COMPARISON OF TRABECULAR BONE MICROARCHITECTURE AND REMODELING IN GLUCOCORTICOID-INDUCED AND POST-MENOPAUSAL OSTEOPOROSIS

Long-term treatment with glucocorticoids (GCs) leads to a rapid bone loss and to a greater risk of fractures. To evaluate the specific effects of this treatment on cancellous bone remodeling, structure, and microarchitecture, we compared 22 transiliac biopsy specimens taken in postmenopausal women (65 +/- 6 years) receiving GCs (> or = 7.5 mg/day, for at least 6 months) and 22 biopsy specimens taken in age-matched women with postmenopausal osteoporosis (PMOP), all untreated and having either at least one vertebral fracture or a T score < -2.5 SD. On these biopsy specimens, we measured static and dynamic parameters reflecting trabecular bone formation and resorption. Also, we performed the strut analysis and evaluated the trabecular bone pattern factor (TBPf), Euler number/tissue volume (E/TV), interconnectivity index (ICI), and marrow star volume (MaSV). Glucocorticoid-induced osteoporosis (GIOP), when compared with PMOP, was characterized by lower bone volume (BV/TV), trabecular thickness (Tb.Th), wall thickness (W.Th), osteoid thickness (O.Th), bone formation rate/bone surface (BFR/BS), adjusted mineral apposition rate/bone surface (Aj.AR/BS), and higher ICI and resorption parameters. After adjustment for BV/TV, the W.Th remained significantly lower in GIOP (p < 0.0001). The active formation period [FP(a+)] was not different. Patients with GIOP were divided into two groups: high cumulative dose GCs (HGCs; 23.7 +/- 9.7 g) and low cumulative dose GCs (LGCs; 2.7 +/- 1.2 g). HGC when compared with LGC was characterized by lower W.Th (p < 0.05), BV/TV (p < 0.001), Tb.Th (p < 0.05), trabecular number (Tb.N; p < 0.05), FP(a+)(p < 0.05), and nodes (p < 0.05), and higher E/TV (p < 0.05), ICI (p < 0.005), and TBPf (p < 0.05). When HGC was compared with PMOP, the results were similar except for the MaSV, which was significantly higher (p < 0.005). In summary, GIOP was characterized by lower formation and higher resorption than in PMOP, already present after LGC. With HGCs, these changes were associated with a more dramatic bone loss caused by a major loss of trabecular connectivity

Increased Gene Expression of RUNX2 and SOX9 in Mesenchymal Circulating Progenitors Is Associated with Autophagy during Physical Activity

Lack of physical exercise is considered an important risk factor for chronic diseases. On the contrary, physical exercise reduces the morbidity rates of obesity, diabetes, bone disease, and hypertension. In order to gain novel molecular and cellular clues, we analyzed the effects of physical exercise on differentiation of mesenchymal circulating progenitor cells (M-CPCs) obtained from runners. We also investigated autophagy and telomerase-related gene expression to evaluate the involvement of specific cellular functions in the differentiation process. We performed cellular and molecular analyses in M-CPCs, obtained by a depletion method, of 22 subjects before (PRE RUN) and after (POST RUN) a half marathon performance. In order to prove our findings, we performed also in vitro analyses by testing the effects of runners' sera on a human bone marrow-derived mesenchymal stem (hBM-MSC) cell line. PCR array analyses of PRE RUN versus POST RUN M-CPC total RNAs put in evidence several genes which appeared to be modulated by physical activity. Our results showed that physical exercise promotes differentiation. Osteogenesis-related genes as RUNX2, MSX1, and SPP1 appeared to be upregulated after the run; data showed also increased levels of BMP2 and BMP6 expressions. SOX9, COL2A1, and COMP gene enhanced expression suggested the induction of chondrocytic differentiation as well. The expression of telomerase-associated genes and of two autophagy-related genes, ATG3 and ULK1, was also affected and correlated positively with MSC differentiation. These data highlight an attractive cellular scenario, outlining the role of autophagic response to physical exercise and suggesting new insights into the benefits of physical exercise in counteracting chronic degenerative conditions

STEAP mRNA detection in serum of patients with solid tumours.

STEAP was identified by the strategy of suppression subtractive hybridizations in Los Angeles prostate cancer xenografts. It is expressed in prostate and other cancers, and not in most normal tissue; it can be used as a marker to evaluate biological samples from individuals suspected of having a disease associated with STEAP dysregulation, such as cancers, and may provide prognostic information useful in defining appropriate therapeutic options. The aim of this study was to test the STEAP mRNA detection in the serum of patients with different malignant tumours by using Real-Time reverse transcription PCR. The results were compared with biological samples obtained by age-matched non-malignant donors. Our data demonstrated that STEAP mRNA is detectable in serum of patients with different solid tumours whereas it is not amplifiable in non-malignant donors. This marker revealed with the molecular method of quantitative PCR in serum, may be useful to discriminate normal and cancer patients