Unique toxin profile of a Mediterranean Ostreopsis cf. ovata strain: HR LC-MS(n) characterization of ovatoxin-f, a new palytoxin congener

Currently, the benthic dinoflagellate Ostreopsis cf. ovata represents a serious concern to human health in the whole Mediterranean basin due to the production of palytoxin congeners, a putative palytoxin and ovatoxins (ovatoxin-a, -b, -c, -d/-e), listed among the most potent marine toxins. High resolution liquid chromatography-mass spectrometry (HR LC-MS) based investigation of a North Western Adriatic strain of Ostreopsis cf. ovata collected at Portonovo (Italy) in 2008 is reported herein. Toxin profile was different from those previously reported for other O. cf. ovata, both qualitatively and quantitatively. For the first time, ovatoxin-a did not dominate the toxin profile, and a new palytoxin congener, here named ovatoxin-f, was detected. Ovatoxin-f and its elemental formula present C(2)H(4) more than ovatoxin-a. HR CID MS(n) experiments allowed us to restrict structural differences between ovatoxin-a and -f to the region between C-95 and C-102, a region not previously been described to be modified in other palytoxins. Ovatoxin-f represents the major component of the toxin profile of the analyzed strain accounting for 50% of the total toxin content, while ovatoxin-a, the dominant toxin in most of the Mediterranean O. cf. ovata strains we have analyzed so far, is the second major component of the toxin profile (23%). Thus, the presence of ovatoxin-f should be taken into account when monitoring programs for palytoxin-like compounds in microalgae and/or seawater are carried out.     

Arterial thrombosis and acute myocardial infarction with angiographically normal coronary arteries in a woman heterozygous for both factor V Leiden and prothrombin mutation

Thirteen years after her last thrombotic event, anticoagulation was discontinued in a patient with combined thrombophilia involving mutation in factor V and G20210A polymorphism of the prothrombin gene. The only history was of arterial thrombosis. Three months later she presented a transmural myocardial infarction caused by coronary thrombosis.     

Ischemia/reperfusion injury and cardioprotective mechanisms: Role of mitochondria and reactive oxygen species

Reperfusion therapy must be applied as soon as possible to attenuate the ischemic insult of acute myocardial infarction(AMI).However reperfusion is responsible for additional myocardial damage,which likely involves opening of the mitochondrial permeability transition pore(mPTP).In reperfusion injury,mitochondrial damage is a determining factor in causing loss of cardiomyocyte function and viability.Major mechanisms of mitochondrial dysfunction include the long lasting opening of mPTPs and the oxidative stress resulting from formation of reactive oxygen species(ROS).Several signaling cardioprotective pathways are activated by stimuli such as preconditioning and postconditioning,obtained with brief intermittent ischemia or with pharmacological agents.These pathways converge on a common target,the mitochondria,to preserve their function after ischemia/reperfusion.The present review discusses the role of mitochondria in cardioprotection,especially the involvement of adenosine triphosphate-dependent potassium channels,ROS signaling,and the mPTP.Ischemic postconditioning has emerged as a new way to target the mitochondria,and to drastically reduce lethal reperfusion injury.Several clinical studies using ischemic postconditioning during angioplasty now support its protective effects,and an interesting alternative is pharmacological postconditioning.In fact ischemic postconditioning and the mPTP desensitizer,cyclosporine A,have been shown to induce comparable protection in AMI patients.     

The sound of consciousness: neural underpinnings of auditory perception

The neural correlates of consciousness (NCC), i.e., patterns of brain activity that specifically accompany a particular conscious experience, have been investigated mainly in the visual system using particularly suited paradigms, such as binocular rivalry and multistable percepts in combination with neural recordings or neuroimaging. Through the same principles, we look here for possible NCC in the auditory modality exploiting the properties of the Deutsch's illusion, a stimulation condition in which a sequence of two specular dichotic stimuli presented in alternation causes an illusory segregation of pitch and side (ear of origin), which can yield up to four different auditory percepts per dichotic stimulus. Using magnetoencephalography in humans, we observed cortical activity specifically accompanying conscious experience of pitch inside an early bilateral network, including the Heschl's gyrus, the middle temporal gyrus, the right inferior, and the superior frontal gyri. The conscious experience of perceived side was instead accompanied by later activity observed bilaterally in the inferior parietal lobe and in the superior frontal gyrus. These results suggest that the NCC are not independent of stimulus features and modality and that, even at the higher cortical levels, the different aspects of a single perceptual scene may not be simultaneously processed.     

The role of genes and environment in shaping co-occurrence of DSM-IV defined anxiety dimensions among Italian twins aged 8–17

This study investigated the ultimate causes of co-variation between symptoms of four common DSM-IV anxiety dimensions – Generalized Anxiety, Panic, Social Phobia and Separation Anxiety disorder – assessed with the Italian version of the Screen for Child Anxiety-Related Emotional Disorders questionnaire in a sample of 378 twin pairs aged 8–17 from the population-based Italian Twin Register. Genetic and environmental proportions of covariance between the targeted anxiety dimensions were estimated by multivariate twin analyses. Genetic influences (explaining from 58% to 99% of covariance) and unique environmental factors were the sole sources of co-variation for all phenotypes under study. Genetic influences associated with different anxiety dimensions coincide remarkably, as indicated by genetic correlations ranging from 0.40 to 0.61, while unique environmental overlap is less substantial. Thus, while additive genetic effects are important in explaining why children report symptoms from multiple anxiety disorders, environmental idiosyncratic factors seem to play a marginal role in shaping the co-occurrence of different anxiety dimensions in childhood.     

Improved retroviral suicide gene transfer in colon cancer cell lines after cell synchronization with methotrexate

Background

Breast cancer is one of the most diagnosed cancers in females, frequently with fatal outcome, so that new strategies for modulating cell proliferation in the mammary tissue are urgently needed. There is some, as yet inconclusive evidence that α-amylase may constitute a novel candidate for affecting cellular growth.

Methods

The present investigation aimed to examine if salivary α-amylase, an enzyme well known for the metabolism of starch and recently introduced as a stress marker, is able to exert antiproliferative effects on the growth of mammary gland epithelial cells. For this purpose, primary epithelial cultures of breast tissue from two different inbred rat strains, Fischer 344 (F344) and Lewis, as well as breast tumor cells of human origin were used. Treatment with human salivary α-amylase was performed once daily for 2 days followed by cell counting (trypan blue assay) to determine alterations in cell numbers. Cell senescence after α-amylase treatment was assessed by β-galactosidase assay. Endogenous α-amylase was detected in cells from F344 and Lewis by immunofluorescence.

Results

Salivary α-amylase treatment in vitro significantly decreased the proliferation of primary cells from F344 and Lewis rats in a concentration-dependent manner. Noticeably, the sensitivity towards α-amylase was significantly higher in Lewis cells with stronger impact on cell growth after 5 and 50 U/ml compared to F344 cells. An antiproliferative effect of α-amylase was also determined in mammary tumor cells of human origin, but this effect varied depending on the donor, age, and type of the cells.

Conclusions

The results presented here indicate for the first time that salivary α-amylase affects cell growth in rat mammary epithelial cells and in breast tumor cells of human origin. Thus, α-amylase may be considered a novel, promising target for balancing cellular growth, which may provide an interesting tool for tumor prophylaxis and treatment.     

MDR-1 gene polymorphisms G2677T and C3435T in a case of Hodgkin's variant of Richter's syndrome

Richter's syndrome is defined as the transformation of low-grade lymphoma to a more aggressive high-grade malignant form, usually diffuse large B-cell lymphoma. Hodgkin's lymphoma variant of Richter transformation is relatively rare, and only approximately 100 cases have been reported in the literature. This study examined a case of a 53-year-old woman who developed Hodgkin's lymphoma almost 5 years after the diagnosis of chronic lymphocytic leukemia (CLL). The major points of interest regarding CLL with Hodgkin's transformation were also considered, such as the potential role of MDR-1 gene polymorphisms. The patient was evaluated for two MDR-1 gene polymorphisms, G2677T polymorphism in exon 21 and silent C3435T polymorphism in exon 26, to ascertain whether polymorphisms affect the risk of Hodgkin's lymphoma variant of Richter transformation and whether genomic polymorphisms provide prognostic information on the clinical progression of the disease. According to the data obtained, the analysis of polymorphisms in the MDR1 gene exons 21 and 26 revealed that the T2677T and T3435T alleles are not a predisposing factor to Richter transformation, while the presence of the wild-type genotype may be associated with a more favorable response to therapy.     

Liver morphologic analysis in perinatal autopsies with intrauterine stress liver morphology in perinatal autopsies

Quantify steatosis, fibrosis, and focuses of extramedullary erythropoiesis (ER) in the liver and report it to the causes of death in the perinatal. Morphologic analysis of steatosis', percentage of fibrosis, and ER of 467 perinatal autopsies. Cases with hypoxia/perinatal anoxia and ascending infection showed higher percentage of fibrosis. The number of ER was significantly higher among premature infants and in cases with infection. Our results contribute to a better quality of perinatal care through clinical demonstration of which injuries are associated with them, what may help in early diagnosis of these alterations in children who survive.