Long-term dietary extra-virgin olive oil rich in polyphenols reverses age-related dysfunctions in motor coordination and contextual memory in mice: role of oxidative stress.

The aim of this study was to evaluate the effects of olive oil phenols on brain aging in mice and to verify whether the antioxidant and antiinflammatory activities of these polyphenols were involved. C57Bl/6J mice were fed from middle age to senescence with extra-virgin olive oil (10% wt/wt dry diet) rich in phenols (total polyphenol dose/day, 6 mg/kg). Behavioral tests were employed to assess cognitive, motor, and emotional behavior after 6 or 12 months of treatment.

Chronic resveratrol treatment ameliorates cell adhesion and mitigates the inflammatory phenotype in senescent human fibroblasts.

We evaluated the effect of resveratrol on the senescence-associated secretory phenotype (SASP) and on adhesion-related processes in cultured human MRC5 fibroblasts. Presenescent cultures were chronically treated with or without 5 µM resveratrol. The development of SASP in MRC5 fibroblasts approaching senescence was significantly attenuated by resveratrol treatment, which reduced both gene expression and release of proinflammatory cytokines.

Transient receptor potential ankyrin 1 channel localized to non-neuronal airway cells promotes non-neurogenic inflammation.

Background: The transient receptor potential ankyrin 1 (TRPA1) channel, localized to airway sensory nerves, has been proposed to mediate airway inflammation evoked by allergen and cigarette smoke (CS) in rodents, via a neurogenic mechanism. However the limited clinical evidence for the role of neurogenic inflammation in asthma or chronic obstructive pulmonary disease raises an alternative possibility that airway inflammation is promoted by non-neuronal TRPA1.

Methodology/principal Findings: By using Real-Time PCR and calcium imaging, we found that cultured human airway cells, including fibroblasts, epithelial and smooth muscle cells express functional TRPA1 channels.

Can estragole in fennel seed decoctions really be considered a danger for human health? A fennel safety update.

Fennel (Foeniculum vulgare Mill.) mature fruit (commonly known as seeds) and essential oil of fennel are widely used as flavoring agents in food products such as liqueurs, bread, cheese, and an ingredient of cosmetics and pharmaceutical products. Moreover fennel infusions are the classical decoction for nursing babies to prevent flatulence and colic spasm.

The modular nature of dendritic cell responses to commensal and pathogenic fungi.

The type of adaptive immune response following host-fungi interaction is largely determined at the level of the antigen-presenting cells, and in particular by dendritic cells (DCs). The extent to which transcriptional regulatory events determine the decision making process in DCs is still an open question. By applying the highly structured DC-ATLAS pathways to analyze DC responses, we classified the various stimuli by revealing the modular nature of the different transcriptional programs governing the recognition of either pathogenic or commensal fungi.

Activation of TRPA1 on dural afferents: a potential mechanism of headache pain.

Activation of transient receptor potential ankyrin-1 (TRPA1) on meningeal nerve endings has been suggested to contribute to environmental irritant-induced headache, but this channel may also contribute to other forms of headache, such as migraine. The preclinical studies described here examined functional expression of TRPA1 on dural afferents and investigated whether activation of TRPA1 contributes to headache-like behaviors. Whole-cell patch-clamp recordings were performed in vitro with 2 TRPA1 agonists, mustard oil (MO), and the environmental irritant umbellulone (UMB) on dural-projecting trigeminal ganglion neurons.

Assessing pain in hospital in-patients: a cross-sectional study in Tuscany, Italy.

Guidelines Towards a Pain-Free Hospital, published in 2001 in Italy, determined an increasing spread of No-Pain Hospital Committees across the country and supported a more effective pain control in hospital. However, few hospitals adopted such protocols. To date, a thorough investigation on quality of pain management documentation is lacking.

Pancreatitis and pancreatic cancer risk: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4).

Background: Pancreatitis is a known risk factor for pancreatic cancer; however, an unknown fraction of the disease is thought to be a consequence of tumor-related duct obstruction.

Patients And Methods: A pooled analysis of a history of pancreatitis and risk of pancreatic cancer was carried out considering the time interval between diagnoses and potential modification by covariates. Adjusted pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from 10 case-control studies (5048 cases of ductal pancreatic adenocarcinoma and 10,947 controls) taking part in the International Pancreatic Cancer Case-Control Consortium (PanC4).

Relaxant effect of a water soluble carbon monoxide-releasing molecule (CORM-3) on spontaneously hypertensive rat aortas.

Purpose: Both carbon monoxide (CO) and nitric oxide (NO) are two gaseous molecules performing relevant functions in mammals. In order to better understand their actions in the cardiovascular system, we have investigated the effects of CORM-3, (tricarbonylchloro(glycinato)ruthenium(II), a water soluble CO-releasing molecule and SNAP (S-nitroso-N-acetyl-DL-penicillamine, a well known NO-releasing molecule) on aortas of normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR).

Methods: The isometric contraction of angiotensin II (AT-II) and endothelin-1 (ET-1) was evaluated in endothelium-denuded aortic strips.

Electron spin resonance measurement of radical scavenging activity of Aronia melanocarpa fruit juice.

Background: The fruits of Aronia melanocarpa (Michx.) Elliot contain large amounts of phenolic substances, mainly procyanidins, anthocyanins and other flavonoids, and phenolic acids. The ability of phenolic substances to act as antioxidants has been well established.

Antioxidant vitamins and mineral supplementation, life span expansion and cancer incidence: a critical commentary.

Purpose: Experimental evidence indicates a strong connection between oxidative damage, cancer, and aging. Epidemiological observations suggest that a diet rich in fruits and vegetables is associated with lower incidence of some cancers and longer life expectancy; since fruits and vegetables contain natural antioxidants, a considerable effort has been dedicated to understanding their effects in experimental studies and in human trials.

Results: A: Effects of antioxidant-containing food and supplements on oxidation damage in humans.

Mild activation of poly(ADP-ribose) polymerase (PARP) is neuroprotective in rat hippocampal slice models of ischemic tolerance.

Ischemic tolerance is a phenomenon in which exposure to a mild preconditioning stress results in resistance to a subsequent lethal ischemic insult. Here we investigated the role of poly(ADP-ribose) polymerase (PARP) in the development of ischemic tolerance by using organotypic rat hippocampal slices exposed to 30 min oxygen-glucose deprivation (OGD), which leads to selective injury of the CA1 subregion 24 h later. We developed models of pharmacological preconditioning by exposing slices to subtoxic concentrations of either N-methyl-D-aspartate (NMDA) or (S)-3,5-dihydroxyphenylglycine (DHPG) and then, 24 h later, to 30 min OGD.

Pharmacologically active microcarriers for endothelial progenitor cell support and survival.

The regenerative potential of endothelial progenitor cell (EPC)-based therapies is limited due to poor cell viability and minimal retention following application. Neovascularization can be improved by means of scaffolds supporting EPCs. The aim of the present study was to investigate whether human early EPCs (eEPCs) could be efficiently cultured on pharmacologically active microcarriers (PAMs), made with poly(d,l-lactic-coglycolic acid) and coated with adhesion/extracellular matrix molecules.

The role of cannabinoids in inflammatory modulation of allergic respiratory disorders, inflammatory pain and ischemic stroke.

This review is intended to offer updated information on the involvement of cannabinoids in the process of inflammation, focusing on immune/allergic reactions, inflammatory pain and neuroinflammation and discussing the interactions among endocannabinoid metabolism, prostanoids and nitric oxide. Two types of cannabinoid receptors, CB1 and CB2, which belong to the G protein-coupled receptor family, have been identified and are targeted by numerous exogenous and endogenous ligands. The activation of CB2 receptors on mast cells has direct antiinflammatory effects, causing decreased release of pro-inflammatory mediators by these cells.

Use of antidepressant serotoninergic medications and cardiac valvulopathy: a nested case-control study in the health improvement network (THIN) database.

Aims: To quantify the risk of cardiac valvulopathy (CV) associated with the use of antidepressant serotoninergic medications (SMs).

Methods: We conducted a case-control study nested in a cohort of users of antidepressant SMs selected from The Health Improvement Network database. Patients who experienced a CV event during follow-up were cases.

A computational pipeline to discover highly phylogenetically informative genes in sequenced genomes: application to Saccharomyces cerevisiae natural strains.

The quest for genes representing genetic relationships of strains or individuals within populations and their evolutionary history is acquiring a novel dimension of complexity with the advancement of next-generation sequencing (NGS) technologies. In fact, sequencing an entire genome uncovers genetic variation in coding and non-coding regions and offers the possibility of studying Saccharomyces cerevisiae populations at the strain level. Nevertheless, the disadvantageous cost-benefit ratio (the amount of details disclosed by NGS against the time-expensive and expertise-demanding data assembly process) still precludes the application of these techniques to the routinely assignment of yeast strains, making the selection of the most reliable molecular markers greatly desirable.

TRPA1 and TRPV4 mediate paclitaxel-induced peripheral neuropathy in mice via a glutathione-sensitive mechanism.

Paclitaxel produces a sensory neuropathy, characterized by mechanical and cold hypersensitivity, which are abated by antioxidants. The transient receptor potential vanilloid 4 (TRPV4) channel has been reported to contribute to paclitaxel-evoked allodynia in rodents. We recently showed that TRP ankyrin 1 (TRPA1) channel mediates oxaliplatin-evoked cold and mechanical allodynia, and the drug targets TRPA1 via generation of oxidative stress.

Topical mannitol reduces inflammatory edema in a rat model of arthritis.

The hexahydric alcohol mannitol is widely used to shift fluids from the intracellular to the extracellular compartments, to increase diuresis and improve mucus clearance in the airways. In principle, because of its physicochemical properties, topical mannitol might also draw fluids out of epidermis or mucosa. Here, we report that topical mannitol applications on the hind paws of rats with adjuvant-induced arthritis reduced paw thickness and tissue edema without affecting the inflammatory infiltrates.

Antidromic vasodilatation and the migraine mechanism.

Despite the fact that an unprecedented series of new discoveries in neurochemistry, neuroimaging, genetics and clinical pharmacology accumulated over the last 20 years has significantly increased our current knowledge, the underlying mechanism of the migraine headache remains elusive. The present review article addresses, from early evidence that emerged at the end of the nineteenth century, the role of 'antidromic vasodilatation' as part of the more general phenomenon, currently defined as neurogenic inflammation, in the unique type of pain reported by patients suffering from migraine headaches. The present paper describes distinctive orthodromic and antidromic properties of a subset of somatosensory neurons, the vascular- and neurobiology of peptides contained in these neurons, and the clinical-pharmacological data obtained in recent investigations using provocation tests in experimental animals and human beings.

Targeting poly(ADP-ribose) polymerase-1 as a promising approach for immunomodulation in multiple sclerosis?

Despite significant advancement in developing therapies for multiple sclerosis (MS), drugs that cure this devastating disorder are an unmet need. Among the remedies showing efficacy in preclinical MS models, inhibitors of poly(ADP-ribose) polymerase (PARP)-1 have gained great momentum. Emerging evidence demonstrates that PARP-1 inhibitors epigenetically regulate gene expression and finely tune transcriptional activation in immune and neural cells.

A snapshot of chemoresistance to PARP inhibitors.

The exploitation of synthetic lethality in BRCA-deficient tumor carriers using potent inhibitors of the enzyme poly(ADP-ribose) polymerase (PARP)-1 has led to an enthusiastic response among basic scientists, oncologists and pharmaceutical companies. However, accumulating evidence demonstrates that resistance to these drugs develops in tumors in both preclinical and clinical settings. Here, I focus on literature dealing with resistance to these drugs and discuss the molecular mechanisms involved, such as restoration of BRCA function, upregulation of nonhomologous end-joining-dependent DNA repair, induction of P-glycoprotein expression and epigenetic deregulation.

The difficulties of polytherapy: examples from antimicrobial chemotherapy.

Medical therapy in patients with more than one pathology means using more pharmaceuticals, which results in a higher risk of drug interactions which are modifications in the action of one drug when it is administered in the presence of another. The consequences can be diminished therapeutic effect or increased adverse reactions. The pharmacological interactions can be either physico-chemical, pharmacokinetic or pharmacodynamic, on the basis of their mechanisms.

The 'headache tree' via umbellulone and TRPA1 activates the trigeminovascular system.

The California bay laurel or Umbellularia californica (Hook. & Arn.) Nutt.

Ecto-ATPase inhibition: ATP and adenosine release under physiological and ischemic in vivo conditions in the rat striatum.

In the central nervous system (CNS) ATP and adenosine act as transmitters and neuromodulators on their own receptors but it is still unknown which part of extracellular adenosine derives per se from cells and which part is formed from the hydrolysis of released ATP. In this study extracellular concentrations of adenosine and ATP from the rat striatum were estimated by the microdialysis technique under in vivo physiological conditions and after focal ischemia induced by medial cerebral artery occlusion. Under physiological conditions, adenosine and ATP concentrations were in the range of 130 nmol/L and 40 nmol/L, respectively.

Assessing 5-year incidence rates and determinants of osteoporotic fractures in primary care.

Purpose: To assess the gender and age-related 5-year incidence rates of osteoporotic fractures, and their related predictors, in a primary care setting.

Methods: We obtained information from the Health Search-CSD Longitudinal Patients Database (HSD). This is an Italian General Practice data repository which comprises information given by computer-based patient records of a selected group of over 900 Primary Care Physicians (PCPs).