249 research outputs found

    La balena fossile di Montopoli in Val d’Arno (Pisa)

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    In Montopoli in Val d’Arno (Pisa Province), where was also found the Idiocetus guicciardinii holotype kept in Florence, is the “Museo Civico di Palazzo Guicciardini” whose paleontological section exhibits a Pliocene specimen of right whale (Eubalaena sp.). This fragmentary remain, found in the Montopoli area in 1974-75 by a local archaeological group, is presented as it was in its outcropping place, together with mollusc shells and mastodon bones. Interesting the white shark tooth found nearby the whale bones suggesting a possible attack or scavenging by the predator

    Unexpected Baclofen Subdural Infusion in a Patient who Carries an Internal Pump for Intrathecal Infusion: A Case Report

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    Objective: We report a case of intrathecal baclofen infusion pump implantation complicated by migration of the catheter tip. Subdural migration, of the intrathecal catheter tip, in who has been having an infusion pump for years and is experiencing swinging dosage related effects it is not the first thing one takes into consideration. A case of subdural migration of intrathecal catheters is presented. Methods: Subsequent X-ray and computed tomography evaluations of the catheter system revealed pooling of contrast medium outside of the intrathecal space, in the lumbar subdural region of the vertebral channel and therefore migration of the pump catheter tip. Results: The spinal catheter was subsequently revised, and the patient made a full recovery. From few days after surgery, the patients spasticity improved and up to now (six months later), he has been experiencing no further complications, is requiring an average baclofen dosage of 150 mcg/day. Conclusion: The possible migration of an intrathecal catheter into the subdural space should be included as differential diagnosis in a patient who experiences a lack of drug effect, despite increases in dosage, after years from pump implantation. We recommend the use of the CT scan, after contrast injection, to detect the distal catheter tip and confirm a normal diffusion into the subarachnoid space

    CURCUMIN INCREASES SENSITIVITY OF RESISTANT OVARIAN TUMOUR CELLS TO PLATINUM DRUGS: APOPTOTIC EFFECTS AND CELL-CYCLE ALTERATIONS.

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    Cisplatin (CDDP) and oxaliplatin are first-line drugs in treatment of many types of epithelial cancer and their combination with other cytostatics are under investigation to limit side effects and resistance to them in clinical therapy of ovarian cancer1. New strategies to improve clinical response and to reduce toxicity of cancer therapy focus on chemoprevention, which hopes to identify substances that can suppress transformation of initiated or precancerous cells to malignant ones 2. To improve the platinum drugs' pharmacological profile, combination with resistance modulators or newly molecularly targeted drugs are under preclinical and clinical investigation. Alteration of appropriate cell-cycle progression and of closely related apoptotic process is a basic feature of tumour cells, and development of new tumour-targeted agents focus on apoptosis, either during cell-cycle arrest or following premature cell-cycle checkpoint exit. Increasingly epidemiological, experimental and clinical trials suggest study the effect of curcumin, the principal curcuminoid of the popular Indian curry spice turmeric, on numerous diseases including multiple myeloma, pancreatic cancer, myelodysplastic syndromes, colon cancer 3. Curcumin protects against cancer, not only because of its well-known antioxidant properties, but also because it modulates intracellular signalling, which is related to cell proliferation and apoptosis 4. OBJECTIVES: The aim of this study was to evaluate the efficacy of a combined treatment using curcumin with cisplatin or with oxaliplatin in a human ovarian cancer cell line (2008) and in its cisplatin-resistant variant (C13) mainly on cell viability, and cell cycling and apoptosis measured by flow cytometry. RESULTS: Curcumin per se caused significant concentration-dependent (0.1-100 M) and time-persistent (24-72 h) reduction of cell proliferation, altered cell-cycle phases and induced apoptosis, as well as it caused ROS generation and altered intracellular glutathione content both in wild type and in CDDP-resistant cancer cell lines. When carcinoma cells were simultaneously exposed to curcumin and to CDDP or to oxaliplatin (at concentrations lower than IC50) cancer cell viability was reduced more than with single-drug treatment. Moreover, dose and time related effects of curcumin, when combined with platinum drugs, were linked to consistent reduction in cell cycling and increased apoptosis, in comparison with single-drug treatment. These effects were significant both in wild type and in CDDP-resistant cells, indicating that curcumin was also able to increase the sensitivity of resistant ovarian cancer cells to cisplatin. CONCLUSIONS: The data suggests that curcumin is a natural compound of potential interest in combination with platinum drugs possibly limiting side effects and resistance and increasing the clinical impact of chemotherapy in ovarian cancer patients. 1. Högberg T, Glimelius B, Nygren P (2001). A systematic overview of chemotherapy effects in ovarian cancer. Acta Oncol.;40(2-3):340-60. 2. Howells LM, Manson MM (2005) Prospects for plant-derived chemopreventive agents exhibiting multiple mechanisms of action. Curr. Med. Chem. Anticancer Agents 5, 201–213. 3. Hatcher H, Planalp R, Cho J, Torti FM, Torti SV (2008). "Curcumin: from ancient medicine to current clinical trials". Cell. Mol. Life Sci. 65 (11): 1631–52. 4. Montopoli M, Ragazzi E, Froldi G, Caparrotta L. (2009) Cell cycle inhibition and apoptosis induced by curcumin combined with cisplatin or oxaliplatin in human ovarian carcinoma cell lines. Cell Proliferation 42(2):195-206

    Plant-derived polyphenols and intestinal HT-29 cells: understanding the cellular uptake.

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    The polyphenols have aroused great scientific interest, since their beneficial effects are attributed to their antioxidant activity: the phenolic compounds can act as metal chelators, antimicrobial agents, radical scavengers, and might also trigger changes in cells and in the signaling pathways, as by preventing the LDL oxidation, platelet aggregation, and ROS generation. The health effects of polyphenols depend also on their bioavailability, which can vary greatly because of different factors, as the degree of hydroxylation, the molecular conformation, etc. A critical point in the debate on health effects of polyphenols is indeed their bioavailability, therefore we used the human colorectal carcinoma cells (HT-29), which are a reference model of intestinal cells, to evaluate the polyphenols ability to pass through the cellular membrane and permeate into the cell. The polyphenols studied in this research are from medicinal plants widely used in traditional medicine: baicalein (from Scutellaria baicalensis G.), eupatorin (Eupatorium semiserratum DC.), galangin (Alpinia officinarum L.), magnolol (Magnolia officinalis L.), myricetin (Myrica rubra S. Z.), oleuropein (Olea europaea L.) and silybin (Silybum marianum L.)

    Mitochondrial Involvement in Cisplatin Resistance

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    Cisplatin is one of the worldwide anticancer drugs and, despite its toxicity and frequent recurrence of resistance phenomena, it still remains the only therapeutic option for several tumors. Circumventing cisplatin resistance remains, therefore, a major goal for clinical therapy and represents a challenge for scientific research. Recent studies have brought to light the fundamental role of mitochondria in onset, progression, and metastasis of cancer, as well as its importance in the resistance to chemotherapy. The aim of this review is to give an overview of the current knowledge about the implication of mitochondria in cisplatin resistance and on the recent development in this research field. Recent studies have highlighted the role of mitochondrial DNA alterations in onset of resistance phenomena, being related both to redox balance alterations and to signal crosstalk with the nucleus, allowing a rewiring of cell metabolism. Moreover, an important role of the mitochondrial dynamics in the adaptation mechanism of cancer cells to challenging environment has been revealed. Giving bioenergetic plasticity to tumor cells, mitochondria allow cells to evade death pathways in stressful conditions, including chemotherapy. So far, even if the central role of mitochondria is recognized, little is known about the specific mechanisms implicated in the resistance. Nevertheless, mitochondria appear to be promising pharmacological targets for overcoming cisplatin resistance, but further studies are necessary

    Cinetica dell'alcol etilico: fattori di variabilità in relazione agli effetti benefici e tossici

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    Wine and alcoholic beverages have a social and symbolic value which is ingrained in the Italian culture, despite the potential adverse effects induced by their consumption. This paper describes the kinetics of alcohol: absorption, distribution, and elimination of ethanol determine the time-course of alcohol concentrations in blood after intake of alcoholic beverages and the degree of exposure of organs to their effects. Most ethanol is eliminated by oxidation to acetaldehyde and acetate, catalysed principally by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Other ethanol oxidation pathways include catalase and cytochrome P450 2E1. Besides being a substrate of CYP2E1, ethanol is also a potent inducer of this enzyme. There is large inter- and intra-individual variability in alcohol metabolism, due to genetic and environmental factors. In particular, gender influences kinetics: in comparison with men, women reach higher concentrations of alcohol in blood after drinking equivalent amounts of alcohol. The difference is partly due to a smaller first-pass metabolism and a lower volume of distribution in women.Immoderate, acute or chronic consumption of alcohol is a well-recognized risk for many diseases. Recent epidemiological studies have given new insights into the public health significance of moderate alcohol consumption: there is evidence that moderate, regular intake of alcohol, particularly red wine, is associated with benefits. The data available in the literature are not conclusive and, in addition, do not adequately assess potential alcohol addiction, which is closely related to detrimental social behaviour and is a risk factor promoting various diseases. The consumption of alcohol cannot be viewed as a benefit for health: it is also important to stress the need for very moderate usage of alcoholic beverages, giving preference to ones containing small quantities of ethanol

    Effetti del concentrato, liofilizzato e alcohol free, da uva rossa fermentata liofenol in modelli in vitro di infiammazione intestinale e neurotossicità

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    Liofenol è un liofilizzato di vino rosso biologico piemontese messo a punto dall’esperienza dell’azienda Ca’ Novella. Liofenol ha ricevuto molta attenzione da parte della comunità scientifica per la sua attività antiproliferativa in vitro (Signorelli et al., 2015) ed antiossidante su modelli animali (Rossi et al., 2016). Negli ultimi anni Liofenol è stato ottimizzato dal punto di vista fitochimico e standardizzato in polifenoli totali (7,5-10% m/m) con alto tenore in resveratrolo, >10 mg/Kg. Sulla base delle indicazioni salutistiche e farmacologiche riguardanti il possibile uso dei polifenoli del vino sui disordini infiammatori e ossidativi, in questo lavoro Liofenol è stato testato in due modelli cellulari: linea epiteliale intestinale Caco-2 e linea neuronale SHSY-5Y. Liofenol, in maniera non concentrazione dipendente, protegge le cellule SHSY-5Y dalla neurotossicità indotta da rotenone. Nella linea Caco-2, Liofenol ha dimostrato possedere un’azione antiossidante riducendo la produzione di radicali liberi dell’ossigeno (ROS) e contrastando la riduzione di resistenza trans-epiteliale del monostrato cellulare indotta da stress ossidativo. Non ha invece mostrato effetti positivi nel contrastare l’azione data da stimolo infiammatorio. In conclusione, Liofenol può essere considerata una innovativa fonte alcohol-free di polifenoli da vino, con un’interessante prospettiva di sviluppo come alimento salutistico pensato per contrastare alterazioni ossidative ed infiammatorie, con particolare riferimento alle problematiche intestinali
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