A survey on the use of antibacterial in orthopaedic surgery

The aim of this study is the comprehensive (pre-operative, operative and post-operative) evaluation of the use of antibacterial drugs on a group of patients subjected to orthopaedical surgery. The data regarding 1000 orthopaedic surgical operations, corresponding to 1000 non-urgent patients, have been examined. This study reveals the incongruity in the use of antibacterial drugs in the orthopaedic surgical activity mainly in operative prophylaxis, but also the administration during the intra operative period, and the use of the same drugs in the post operative perio

Natural function and structural modification of climacostol, a ciliate secondary metabolite

The review highlights the main results of two decades of research on climacostol (5-[(2Z)-non-2-en-1-yl]benzene-1,3-diol), the resorcinolic lipid produced and used by the ciliated protozoan Climacostomum virens for chemical defense against a wide range of predators, and to assist its carnivorous feeding. After the first studies on the physiological function of climacostol, the compound and some analogues were chemically synthesized, thus allowing us to explore both its effect on different prokaryotic and eukaryotic biological systems, and the role of its relevant structural traits. In particular, the results obtained in the last 10 years indicate climacostol is an effective antimicrobial and anticancer agent, bringing new clues to the attempt to design and synthesize additional novel analogues that can increase or optimize its pharmacological properties

Current Evidence for a Role of Neuropeptides in the Regulation of Autophagy

Neuropeptides drive a wide diversity of biological actions and mediate multiple regulatory functions involving all organ systems. They modulate intercellular signalling in the central and peripheral nervous systems as well as the cross talk among nervous and endocrine systems. Indeed, neuropeptides can function as peptide hormones regulating physiological homeostasis (e.g., cognition, blood pressure, feeding behaviour, water balance, glucose metabolism, pain, and response to stress), neuroprotection, and immunomodulation. We aim here to describe the recent advances on the role exerted by neuropeptides in the control of autophagy and its molecular mechanisms since increasing evidence indicates that dysregulation of autophagic process is related to different pathological conditions, including neurodegeneration, metabolic disorders, and cancer

Health effects of living near an incinerator: A systematic review of epidemiological studies, with focus on last generation plants

Huge reductions in incinerators' emissions occurred over time, and results of older studies cannot be directly generalized to modern plants. We conducted a systematic review of the epidemiologic evidence of the health effects of incinerators, classifying plants in three generations, according to emission limits. A systematic search identified 63 epidemiologic studies, published in English, investigating health effects of incinerators on humans. We focused on cancer, cardio-cerebrovascular diseases (CVD) and respiratory diseases, pregnancy outcomes and congenital anomalies. Only six studies in the general population were on third generation incinerators providing data on pregnancy outcomes and congenital anomalies. Given the heterogeneity of methods, the abundance of ecological/semi-ecological studies and the lack of reliable quantitative measures of exposure in several studies we did not perform any meta-analysis. No excesses emerged concerning all cancers and lung cancer. An excess of non-Hodgkin lymphoma was reported in some earlier studies, but not for second generation plants. Possible excesses of soft tissue sarcomas were confined to earlier incinerators and the areas closer to the plants. No clear association emerged for CVD and diseases of the respiratory system. Several different pregnancy outcomes were considered, and no consistent association emerged, in spite of a few positive results. Studies were negative for congenital anomalies as a whole. Sporadic excesses were reported in a few studies for specific types of anomalies, but no consistent pattern emerged. Evaluation of the evidence was hindered by heterogeneity in reporting and classification of outcomes across studies. Direct evidence from third generation plants is scarce. Methodological issues in study design (mainly related to exposure assessment, confounding and ecological design) and analysis make interpretation of results complex. In spite of this, the overall evidence suggests that, if there were any excesses at all for older incinerators, they were modest at most. Additional monitoring of third generation plants needs to overcome methodological weakness

Autophagy-mediated neuroprotection induced by octreotide in an ex vivo model of early diabetic retinopathy

Neuronal injury plays a major role in diabetic retinopathy (DR). Our hypothesis was that the balance between neuronal death and survival may depend on a similar equilibrium between apoptosis and autophagy and that a neuroprotectant may act by influencing this equilibrium. Ex vivo mouse retinal explants were treated with high glucose (HG) for 10days and the somatostatin analog octreotide (OCT) was used as a neuroprotectant. Chloroquine (CQ) was used as an autophagy inhibitor. Apoptotic and autophagic markers were evaluated using western blot and immunohistochemistry. HG-treated explants displayed a significant increase of apoptosis paralleled by a significant decrease of the autophagic flux, which was likely to be due to increased activity of the autophagy regulator mTOR (mammalian target of rapamycin). Treatment with OCT rescued HG-treated retinal explants from apoptosis and determined an increase of autophagic activity with concomitant mTOR inhibition. Blocking the autophagic flux with CQ completely abolished the anti-apoptotic effect of OCT. Immunohistochemical observations showed that OCT-induced autophagy is localized to populations of bipolar and amacrine cells and to ganglion cells. These observations revealed the antithetic role of apoptosis and autophagy, highlighting their equilibrium from which neuronal survival is likely to depend. These data suggest the crucial role covered by autophagy, which could be considered as a molecular target for DR neuroprotective treatment strategies

Determination of the calorimetric energy in extensive air showers

The contribution of different components of an air shower to the total energy deposit in the atmosphere, for different angles and primary particles, was studied using the CORSIKA air shower simulation code. The amount of missing energy, parameterized in terms of the calorimetric energy, was calculated. The results show that this parameterization varies less than 1% with angle or observation level. The dependence with the primary mass is less than 5% and, with the high energy hadronic interaction model, less than 2%. The systematic error introduced by the use of just one parameterization of the missing energy correction function, for an equal mixture of proton and iron at 45deg, was calculated to be below 3%. We estimate the statistical error due to shower-to-shower fluctuations to be about 1%.Comment: 15 pages, 4 figures, 4 tables. This version corresponds to the one aproved for publication in Astroparticle Physic

Acid Sphingomyelinase Downregulation Enhances Mitochondrial Fusion and Promotes Oxidative Metabolism in a Mouse Model of Melanoma

Melanoma is the most severe type of skin cancer. Its unique and heterogeneous metabolism, relying on both glycolysis and oxidative phosphorylation, allows it to adapt to disparate conditions. Mitochondrial function is strictly interconnected with mitochondrial dynamics and both are fundamental in tumour progression and metastasis. The malignant phenotype of melanoma is also regulated by the expression levels of the enzyme acid sphingomyelinase (A-SMase). By modulating at transcriptional level A-SMase in the melanoma cell line B16-F1 cells, we assessed the effect of enzyme downregulation on mitochondrial dynamics and function. Our results demonstrate that A-SMase influences mitochondrial morphology by affecting the expression of mitofusin 1 and OPA1. The enhanced expression of the two mitochondrial fusion proteins, observed when A-SMase is expressed at low levels, correlates with the increase of mitochondrial function via the stimulation of the genes PGC-1alpha and TFAM, two genes that preside over mitochondrial biogenesis. Thus, the reduction of A-SMase expression, observed in malignant melanomas, may determine their metastatic behaviour through the stimulation of mitochondrial fusion, activity and biogenesis, conferring a metabolic advantage to melanoma cells

Climacostol reduces tumour progression in a mouse model of melanoma via the p53-dependent intrinsic apoptotic programme

Climacostol, a compound produced by the ciliated protozoan Climacostomum virens, displayed cytotoxic properties in vitro. This study demonstrates that it has anti-tumour potential. Climacostol caused a reduction of viability/proliferation of B16-F10 mouse melanoma cells, a rapidly occurring DNA damage, and induced the intrinsic apoptotic pathway characterised by the dissipation of the mitochondrial membrane potential, the translocation of Bax to the mitochondria, the release of Cytochrome c from the mitochondria, and the activation of Caspase 9-dependent cleavage of Caspase 3. The apoptotic mechanism of climacostol was found to rely on the up-regulation of p53 and its targets Noxa and Puma. In vivo analysis of B16-F10 allografts revealed a persistent inhibition of tumour growth rate when melanomas were treated with intra-tumoural injections of climacostol. In addition, it significantly improved the survival of transplanted mice, decreased tumour weight, induced a remarkable reduction of viable cells inside the tumour, activated apoptosis and up-regulated the p53 signalling network. Importantly, climacostol toxicity was more selective against tumour than non-tumour cells. The anti-tumour properties of climacostol and the molecular events associated with its action indicate that it is a powerful agent that may be considered for the design of pro-apoptotic drugs for melanoma therapy