215 research outputs found

    Deep sea as a source of novel-anticancer drugs

    Get PDF
    The deep-sea habitat is a source of very potent marine-derived agents that may inhibit the growth of human cancer cells “in vitro” and “in vivo”. Salinosporamide-A, Marizomib, by Salinispora species is a proteasome inhibitor with promising anticancer activity (Phase I/II trials). Different deep-sea-derived drugs are under preclinical evaluation. Cancer is a complex disease that may be represented by network medicine. A simple consequence is the change of the concept of target entity from a single protein to a whole molecular pathway and or cellular network. Deep-sea-derived drugs fit well to this new concept

    Kinematic analysis of reaching movements of the upper limb after total or reverse shoulder arthroplasty

    Get PDF
    Studies have analyzed three-dimensional complex motion of the shoulder in healthy subjects or patients undergoing total shoulder arthroplasty (TSA) or reverse shoulder arthroplasty (RSA). No study to date has assessed the reaching movements in patients with TSA or RSA. Twelve patients with TSA (Group A) and 12 with RSA (Group B) underwent kinematic analysis of reaching movements directed at four targets. The results were compared to those of 12 healthy subjects (Group C). The assessed parameters were hand-to-target distance, target-approaching velocity, humeral-elevation angular velocity, normalized jerk (indicating motion fluidity), elbow extension and humeral elevation angles. Mean Constant score increased by 38 points in Group A and 47 in Group B after surgery. In three of the tasks, there were no significant differences between healthy subjects and patients in the study groups. Mean target-approaching velocity and humeral-elevation angular velocity were significantly greater in the control group than in study groups and, overall, greater in Group A than Group B. Movement fluidity was significantly greater in the controls, with patients in Group B showing greater fluidity than those in Group A. Reaching movements in the study groups were comparable, in three of the tasks, to those in the control group. However, the latter performed significantly better with regard to target-approaching velocity, humeral-elevation angular velocity and movement fluidity, which are the most representative characteristics of reaching motion. These differences, that may be related to deterioration of shoulder proprioception after prosthetic implant, might possibly be decreased with appropriate rehabilitation

    The interplay of reactive oxygen species, hypoxia, inflammation, and sirtuins in cancer initiation and progression

    Get PDF
    The presence of ROS is a constant feature in living cells metabolizing O2. ROS concentration and compartmentation determine their physiological or pathological effects. ROS overproduction is a feature of cancer cells and plays several roles during the natural history of malignant tumor. ROS continuously contribute to each step of cancerogenesis, from the initiation to the malignant progression, acting directly or indirectly. In this review, we will (a) underline the role of ROS in the pathway leading a normal cell to tumor transformation and progression, (b) define the multiple roles of ROS during the natural history of a tumor, (c) conciliate many conflicting data about harmful or beneficial effects of ROS, (d) rethink the importance of oncogene and tumor suppressor gene mutations in relation to the malignant progression, and (e) collocate all the cancer hallmarks in a mechanistic sequence which could represent a "physiological" response to the initial growth of a transformed stem/pluripotent cell, defining also the role of ROS in each hallmark. We will provide a simplified sketch about the relationships between ROS and cancer. The attention will be focused on the contribution of ROS to the signaling of HIF, NFÎşB, and Sirtuins as a leitmotif of cancer initiation and progressi

    The strength of crystalline color superconductors

    Full text link
    We present a study of the shear modulus of the crystalline color superconducting phase of quark matter, showing that this phase of dense, but not asymptotically dense, quark matter responds to shear stress as a very rigid solid. This phase is characterized by a gap parameter Δ\Delta that is periodically modulated in space and therefore spontaneously breaks translational invariance. We derive the effective action for the phonon fields that describe space- and time-dependent fluctuations of the crystal structure formed by Δ\Delta, and obtain the shear modulus from the coefficients of the spatial derivative terms. Within a Ginzburg-Landau approximation, we find shear moduli which are 20 to 1000 times larger than those of neutron star crusts. This phase of matter is thus more rigid than any known material in the universe, but at the same time the crystalline color superconducting phase is also superfluid. These properties raise the possibility that the presence of this phase within neutron stars may have distinct implications for their phenomenology. For example, (some) pulsar glitches may originate in crystalline superconducting neutron star cores.Comment: 8 pages, proceedings of QCD@work 2007 International Workshop on QCD Theory and Experiment- Martina Franca (Italy), June 200

    Trimetazidine improves left ventricular function in diabetic patients with coronary artery disease: a double-blind placebo-controlled study

    Get PDF
    BACKGROUND: Patients with diabetic cardiomyopathy have an impaired myocardial glucose handling and distal distribution of coronary atherosclerosis. Trimetazidine, an anti-ischemic metabolic agent, improves myocardial glucose utilization though inhibition of fatty acid oxidation. Aim of the present study was to evaluate whether the metabolic effect of trimetazidine on left ventricular function in patients with diabetic cardiomyopathy. METHODS: 32 patients (24 males and 8 females, mean (SE) age = 67 ± 6 years) with type 2 diabetes and ischemic cardiomyopathy were randomized to receive either trimetazidine (20 mg, t.d.s.) or placebo (t.d.s.) for six months in a randomized parallel study. Patients performed an echocardiogram at baseline and after 6 months. RESULTS: Demographic data were comparable between the two groups. After six month baseline left ventricular end-diastolic diameters increased from 62.4 ± 1.7 to 63 ± 2.1 mm in the placebo group, while decreased from 63.2 ± 2.1 to 58 ± 1.6 mm (p < 0.01 compared to baseline) in the trimetazidine group. Compared to baseline, left ventricular ejection fraction increased by 5.4 ± 0.5% (p < 0.05) in the trimetazidine group while remained unchanged in the placebo group -2.4 ± 1.1% (NS), p < 0.01 between groups. A significant improvement in wall motion score index and in the E/A wave ratio was detected in patients treated with trimetazidine, but not in those receiving placebo. CONCLUSION: in diabetic patients with ischemic heart disease trimetazidine added to standard medical therapy has beneficial effect on left ventricular volumes and on left ventricular ejection fraction compared to placebo. This effect may be related to the effect of trimetazidine upon cardiac glucose utilization

    Subacute copper-deficiency myelopathy in a patient with occult celiac disease

    Get PDF
    Context: Acquired copper deficiency represents a rare cause of progressive myelopathy presenting with sensory ataxia and spastic gait. The time interval from neurological symptoms onset to diagnosis of myelopathy ranges from 2 months to several years in almost all cases, mimicking the clinical course of subacute combined degeneration due to vitamin B12 deficiency. Findings: A 60-year-old man, without any gastrointestinal symptoms, developed over the course of one week rapidly progressive gait imbalance, tingling and numbness in his feet and ascending lower limb weakness. Spine magnetic resonance imaging revealed hyperintensity involving cervical and dorsal posterior columns of spinal cord. Blood analysis revealed undetectable serum copper levels, low serum ceruloplasmin and positive serum Immunoglobulin A anti-tissue transglutaminase. Upper gastrointestinal endoscopy was performed revealing duodenal villous atrophy consistent with a malabsorption pattern. A gluten-free diet in association with intravenous then oral copper supplementation prompted sustained normalization of serum copper levels and progressive clinical improvement. Conclusion/Clinical Relevance: We report a rare case of myelopathy induced by copper deficiency secondary to undiagnosed celiac disease, peculiarly presenting with a subacute onset. This case expands the neurological presentation and clinical course of myelopathy due to acquired copper deficiency. We suggest investigation of copper deficiency in patients presenting with subacute or even acute sensory ataxia and spastic gait. Detection of hypocupremia in patients without a previous history of gastric surgery should lead to diagnostic testing for celiac disease even in the absence of any obvious gastrointestinal symptoms

    ERK-1 MAP kinase prevents TNF-induced apoptosis through bad phosphorylation and inhibition of bax translocation in HeLa cells

    Get PDF
    Extracellular signal-regulated kinase (ERK) 1/2 signaling is involved in tumor cell survival through the regulation of Bcl-2 family members. To explore this further and to demonstrate the central role of the mitochondria in the ERK1/2 pathway we used the HeLa cellular model where apoptosis was induced by tumor necrosis factor (TNF) and cycloheximide (CHX). We show that HeLa cells overexpressing ERK-1 displayed resistance to TNF and CHX. HeLa cells overexpressing a kinase-deficient form of ERK-1 (K71R) were more sensitive to TNF and CHX. In the ERK-1 cells, Bad was phosphorylated during TNF + CHX treatment. In the HeLa wt cells and in the K71R clones TNF and CHX decreased Bad phosphorylation. ERK-1 cells treated with TNF and CHX did not release cytochrome c from the mitochondria. By contrast, HeLa wt and K71R clones released cytochrome c. Bax did not translocate to the mitochondria in ERK-1 cells treated with TNF + CHX. Conversely, HeLa wt and K71R clones accumulated Bax in the mitochondria. In the HeLa wt cells and in both ERK-1 transfectants Bid was cleaved and accumulated in the mitochondria. The caspase-8 inhibitor IETD-FMK and the mitochondrial membrane permeabilization inhibitor bongkrekic acid (BK), partially prevented cell death by TNF + CHX. Anisomycin, a c-Jun N-terminal kinases activator, increased TNF-killing. The ERK-1 cells were resistant to TNF and anisomycin, whereas K71R clones resulted more sensitive. Our study demonstrates that in HeLa cells the ERK-1 kinase prevents TNF + CHX apoptosis by regulating the intrinsic mitochondrial pathway through different mechanisms. Inhibition of the intrinsic pathway is sufficient to almost completely prevent cell death. © 2009 Wiley-Liss, Inc

    A meta-analysis of biomarkers related to oxidative stress and nitric oxide pathway in migraine

    Get PDF
    Background Oxidative and nitrosative stress are considered key events in the still unclear pathophysiology of migraine. Methods Studies comparing the level of biomarkers related to nitric oxide (NO) pathway/oxidative stress in the blood/urine of migraineurs vs. unaffected controls were extracted from the PubMed database. Summary estimates of mean ratios (MR) were carried out whenever a minimum of three papers were available. Nineteen studies were included in the meta-analyses, accounting for more than 1000 patients and controls, and compared with existing literature. Results Most studies measuring superoxide dismutase (SOD) showed lower activity in cases, although the meta-analysis in erythrocytes gave null results. On the contrary, plasma levels of thiobarbituric acid reactive substances (TBARS), an aspecific biomarker of oxidative damage, showed a meta-MR of 2.20 (95% CI: 1.65–2.93). As for NOs, no significant results were found in plasma, serum and urine. However, higher levels were shown during attacks, in patients with aura, and an effect of diet was found. The analysis of glutathione precursor homocysteine and asymmetric dimethylarginine (ADMA), an NO synthase inhibitor, gave inconclusive results. Conclusions The role of the oxidative pathway in migraine is still uncertain. Interesting evidence emerged for TBARS and SOD, and concerning the possible role of diet in the control of NOx levels

    rehabilitation in neuro oncology a meta analysis of published data and a mono institutional experience

    Get PDF
    Background. Rehabilitation for cancer patients with central nervous system (CNS) involvement is rarely considered and data on its use are limited. The purpose of the present study is to collect all available published data on neuro-oncology rehabilitation and perform a meta-analysis where results were presented in a comparable manner. Moreover, the authors report results on cancer patients with neurological disabilities undergoing rehabilitation at their unit. Study design. A PubMed search was performed to identify studies regarding cancer patients with CNS involvement undergoing inpatient physical rehabilitation. Studies with a complete functional evaluation at admission and discharge were selected. As the most common evaluation scales were Functional Independence Measure (FIM) and Barthel Index (BI), only articles with complete FIM and/or BI data were selected for the meta-analysis. Moreover, 23 cancer patients suffering from diverse neurological disabilities underwent standard rehabilitation program be..
    • …
    corecore