Human brain networks: a graph theoretical analysis of cortical connectivity normative database from EEG data in healthy elderly subjects

GeroScience - Moving from the hypothesis that aging processes modulate brain connectivity networks, 170 healthy elderly volunteers were submitted to EEG recordings in order to define age-related...     

Olea europea L. Leaves and Hibiscus sabdariffa L. Petals Extracts: Herbal Mix from Cardiovascular Network Target to Gut Motility Dysfunction Application

It is well known that diet and nutrition play a critical role in the etiopathogenesis of many disorders. On the other hand, nutrients or bioactive compounds can specifically target and control various aspects of the mechanism underlying the pathology itself, and, in this context, diseases related to intestinal motility disorders stand out. The Herbal Mix (HM) consisting of Olea europea L. leaf (OEE) and Hibiscus sabdariffa L. (HSE) extracts (13:2) has been proven to be a promising nutraceutical option for many diseases, but its potential in inflammatory-driven gastrointestinal disorders is still unexplored. In this study, HM effects on guinea-pig ileum and colon contractility (induced or spontaneous) and on human iNOS activity, as well as on human colorectal adenocarcinoma Caco-2 cells, were studied. Results showed that the HM can control the ileum and colon contractility without blocking the progression of the food bolus, can selectively inhibit iNOS and possesses a strong pro-apoptotic activity towards Caco-2 cells. In conclusion, the present results suggest that, in some diseases, such as those related to motility disorders, an appropriate nutritional approach can be accompanied by a correct use of nutraceuticals that could help not only in ameliorating the symptoms but also in preventing more severe, cancer-related conditions.     

Cardiotoxicity from Capecitabine Chemotherapy: Prospective Study of Incidence at Rest and During Physical Exercise

BackgroundPhysical activity may increase the risk of cardiotoxicity (myocardial ischemia, major arrhythmias) of 5-Fluorouracil, but this risk has never been investigated for its prodrug capecitabine.Patients and MethodsOne hundred and ninety-two consecutive patients undergoing capecitabine chemotherapy from December 1, 2010 through July 31, 2016 were prospectively evaluated. The baseline evaluation included electrocardiography (ECG) and echocardiography (2DE); a follow-up evaluation, including ECG and exercise stress testing (2DE in case of ECG abnormalities), was done after ≥10 days of treatment. Cardiotoxicity was suspected from ischemic ECG changes, new kinetic abnormalities at 2DE, Lown classification ≥2 ventricular arrhythmia, symptomatic arrhythmias, or positive stress test, and confirmed by a negative stress test after capecitabine washout.ResultsCardiotoxicity was diagnosed in 32 patients (16.7%): six at rest and 26 during exercise. All 32 patients had ECG abnormalities: ST-segment changes (24 patients), negative T-waves (2) and/or arrhythmias: ventricular arrhythmias (14 cases), supraventricular tachycardia (2), complete heart block (1). Eight patients had typical symptoms, 6 had atypical symptoms, 1 had syncope, 17 (53%) were asymptomatic. Cardiotoxicity was more common in patients with atypical symptoms during daily life (OR = 15.7) and in those on a therapeutic schedule of 5 days/week (OR = 9.44).ConclusionCapecitabine cardiotoxicity is frequent, and often elicited by physical effort. Oncologists, cardiologists, and general practitioners should be aware of this risk. Active cardiotoxicity surveillance with ECG (and echocardiogram and/or stress testing in suspected cases) during therapy is recommended.Clinical Trials registration numberCRO-2010-17.     

Radiation effects on development of HER2-positive breast carcinomas.

PURPOSE: Neither hormone-related nor genetics risk factors have been associated with the development of highly proliferative HER2-positive breast carcinomas. Because the majority of HER2-positive tumors present the amplification of the oncogene, we asked whether genomic instability triggered by irradiation might be involved in the induction of HER2-overexpressing breast carcinomas. EXPERIMENTAL DESIGN: Sixty-six infiltrating breast carcinomas from patients treated with radiation therapy for Hodgkin's lymphoma or other pediatric solid tumors and a control series of 61 consecutive sporadic breast tumors were analyzed by immunohistochemistry for HER2 expression with HercepTest. A panel of antibodies against estrogen receptor, progesterone receptor, c-kit, cytokeratin 5/6, p53, and ki67 antigen was also used to identify differentiation subsets and molecular characteristics of the analyzed breast carcinomas. RESULTS: Although no differences between the two tumor series were found with respect to HER2 expression scored 2+ and 3+, the percentage of 3+ HER2-positive tumors was significantly higher in patients irradiated during breast maturation compared with patients irradiated after breast maturation (35.3% versus 12.5%, P = 0.046). In the latter group, 52.5% of the breast carcinomas showed basal-like differentiation (estrogen receptor, progesterone receptor, and HER2 negative) versus only 5.9% in the group irradiated during breast development (P < 0.0001). Analysis adjusted for age confirmed the significant increase in basal-like tumor development in patients irradiated within 4 years of menarche, but also showed that the differences between patients irradiated before and after puberty in HER2 3+ tumor frequencies are due to age-related differences in HER2 3+ tumor onset. CONCLUSION: Together, our data indicate that the development of HER2-positive tumors correlates with timing rather than type of carcinogenic hits and provide clear evidence that radiation is a risk factor for breast carcinomas showing basal-like differentiation.     

The malformation of the cerebellar fissura prima: a tool for studying histogenetic processes

Due to its regular cytoarchitecture and the relatively low number of cell types, the development of the cerebellar cortex is a model of election for studies of morphogenetic processes. To unravel the cellular and molecular mechanisms that regulate cell development, migration and differentiation and the settling of local circuits, pertubation of the three-layered organization of the cerebellar cortex has been induced by X-ray irradiation or antimitotic drug. In this review we deal with some data about the incidence and development of the malformation of the cerebellar fissura prima of the rat, as an eligible model for histogenetic studies. The naturally occurring malformation of the fissura prima is characterized by the loss of the three-layered organization of folia and the presence of large masses of ectopic granule cells. The malformation appears to be under genetic control, since the incidence of affected animals is consistent over extended breeding cycles, although the target of the eventual mutation is unknown. The observation of development of the malformation in infant rats suggests that a defect in meninges, and in particular in the pia mater, is a primary contributing factor. The molecules responsible for this defect are not identified, but they must be involved in basal lamina stabilization or destabilization. In fact, there is evidence that meninges do develop during first stages of histogenesis and only later degenerate. A possible correlation with certain human pathologies that involve defects in foliation is discussed.     

Dopamine inhibits responses of astroglia-enriched cultures to lipopolysaccharide via a beta-adrenoreceptor-mediated mechanism

We here investigated the effect of the catecholaminergic neurotransmitter dopamine (DA), on the release of two major inflammatory effectors, TNF-alpha and nitric oxide, in rat astroglia-enriched cultures stimulated with the bacterial endotoxin lipopolysaccharide (LPS). Upon LPS challenge, we observed a dramatic increase in the culture medium of the TNF-alpha protein, an effect thereafter followed by an increase of nitric oxide synthase type 2 (NOS2) mRNA and, at later times, of nitrite accumulation, an index of nitric oxide (NO) production. DA substantially inhibited the release of TNF-alpha and NO evoked by LPS, an effect not mimicked by selective agonists nor prevented by selective antagonists of the DA receptors. The inhibitory effects of DA were mimicked by noradrenalin and isoproterenol and fully reverted by propranolol, a selective antagonist of the beta-adrenergic receptors. In addition, selective antagonists of beta-adrenergic receptor type 1 (metoprolol) and type 2 (ICI-118,551) counteracted the inhibitory effects of DA on LPS-induced TNF-alpha and NO release. Accordingly, agents capable of elevating intracellular cyclic 3',5'-adenosine monophosphate (cAMP), such as forskolin and dibutyryl-cAMP, mimicked DA inhibitory effects on LPS-evoked accumulation of TNF-alpha and nitrite. These data, consistent with a role of DA as local modulator of glial inflammatory responses, uncover the existence of an interaction between DA and heterologous beta-adrenergic receptors in astroglial cells.     

HIV-associated dementia, Alzheimer's disease, multiple sclerosis, and schizophrenia: gene expression review

RNA and protein gene expression technologies are revolutionizing our view and understanding of human diseases and enable us to analyze the concurrent expression patterns of large numbers of genes. These new technologies allow simultaneous study of thousands of genes and their changes in regulation and modulation patterns in relation to disease state, time, and tissue specificity. This review summarizes the application of this modern technology to four common neurological and psychiatric disorders: HIV-1-associated dementia, Alzheimer's disease, multiple sclerosis, and schizophrenia and is a first comparison of these diseases using this approach.     

In vitro antitumour activity of resveratrol in human melanoma cells sensitive or resistant to temozolomide

Resveratrol, a polyphenol present in many plant species, exhibits a wide range of biological and pharmacological activities both in vitro and in vivo. It has been shown to exert a potent chemopreventive effect in carcinogenesis models and to induce cell growth inhibition and apoptosis in human tumour cells, including melanoma cells. Malignant melanoma is considered to be a chemotherapy-refractory tumour, and the commonly used anticancer drugs do not seem to modify the prognosis of metastatic disease. To further evaluate the therapeutic potential of resveratrol in the treatment of melanoma, we selected three human melanoma cell lines with different levels of resistance to temozolomide (TMZ), an antitumour triazene compound. The cell lines were subjected to resveratrol treatment and analysed for cell growth inhibition, cell cycle perturbation and apoptosis induction. We found that resveratrol markedly impaired proliferation of both the TMZ-sensitive M14 and the TMZ-resistant SK-Mel-28 and PR-Mel cell lines. The latter cell line was two-fold more resistant to the drug than M14 and SK-Mel-28 cells. The sensitivity of normal human keratinocytes to resveratrol was found to be significantly higher than that of M14 and SK-Mel-28 cells and similar to that of the PR-Mel cell line. This suggests a possible good in vivo therapeutic index for resveratrol. Our results also show that the growth-inhibitory effect of resveratrol on melanoma cells is mainly due to its ability to induce S-phase arrest and apoptosis. Taken together, our data indicate that resveratrol is an interesting candidate for the treatment of advanced melanoma.