Activation of retinoid X receptors protects retinal neurons and pigment epithelial cells from BMAA-induced death.

Exposure to the non-protein amino acid cyanotoxin β-N-methylamino-L-alanine (BMAA), released by cyanobacteria found in many water reservoirs has been associated with neurodegenerative diseases. We previously demonstrated that BMAA induced cell death in both retina photoreceptors (PHRs) and amacrine neurons by triggering different molecular pathways, as activation of NMDA receptors and formation of carbamate-adducts was only observed in amacrine cell death. We established that activation of Retinoid X Receptors (RXR) protects retinal cells, including retina pigment epithelial (RPE) cells from oxidative stress-induced apoptosis.

Educational Intervention of Healthy Life Promotion for Children with a Migrant Background or at Socioeconomic Disadvantage in the North of Italy: Efficacy of Telematic Tools in Improving Nutritional and Physical Activity Knowledge.

The aim of the "Smuovi La Salute" ("Shake Your Health") project was to implement an integrated and comprehensive model to prevent and treat overweight and obesity in low socioeconomic status (SES) and minority groups living in three different districts in the north of Italy. An app and a cookbook promoting transcultural nutrition and a healthy lifestyle were developed, and no-cost physical activities were organized. Healthy lifestyle teaching was implemented in 30 primary school classrooms.

Damaging effects of BMAA on retina neurons and Müller glial cells.

B-N-methylamino-L-alanine (BMAA), a cyanotoxin produced by most cyanobacteria, has been proposed to cause long term damages leading to neurodegenerative diseases, including Amyotrophic Lateral Sclerosis/Parkinsonism Dementia complex (ALS/PDC) and retinal pathologies. Previous work has shown diverse mechanisms leading to BMAA-induced degeneration; however, the underlying mechanisms of toxicity affecting retina cells are not fully elucidated. We here show that BMAA treatment of rat retina neurons in vitro induced nuclear fragmentation and cell death in both photoreceptors (PHRs) and amacrine neurons, provoking mitochondrial membrane depolarization.

Agonist Effects of Propranolol on Non-Tumor Human Breast Cells.

The β-blocker propranolol (PROP) has been proposed as a repurposed treatment for breast cancer. The similarity of action between β-agonists and antagonists found on breast cells encouraged us to compare PROP and isoproterenol (ISO, agonist) signaling pathways on a human breast cell line. Cell proliferation was measured by cell counting and DNA-synthesis.

Tacripyrimidines, the first tacrine-dihydropyrimidine hybrids, as multi-target-directed ligands for Alzheimer's disease.

Notwithstanding the combination of cholinesterase (ChE) inhibition and calcium channel blockade within a multitarget therapeutic approach is envisaged as potentially beneficial to confront Alzheimer's disease (AD), this strategy has been scarcely investigated. To explore this promising line, a series of 5-amino-4-aryl-3,4,6,7,8,9-hexahydropyrimido [4,5-b]quinoline-2(1H)-thiones (tacripyrimidines) (4a-l) were designed by juxtaposition of tacrine, a ChE inhibitor (ChEI), and 3,4-dihydropyrimidin-2(1H)-thiones, as efficient calcium channel blockers (CCBs). In agreement with their design, all tacripyrimidines, except the unsubstituted parent compound and its p-methoxy derivative, acted as moderate to potent CCBs with activities generally similar or higher than the reference CCB drug nimodipine and were modest-to-good ChEIs.

[Ethics, medical ethics, and occupational medicine: is their dialogue possible?].

Today's medicine faces some critical moral challenges, yet the medical class suffers from an increasingly evident malaise: a growing dissatisfaction with an ethical demand often perceived as a cumbersome burden of rules and prohibitions, which risk to erode the fiduciary relations with patients. Such a negative appraisal is partly due to a narrow interpretation of the meaning of ethics, a misconception whose roots are in the positivistic stance that permeates our culture, and in its almost exclusively technological bent. This radical orientation of our culture shows itself in the vanishing of the idea of an intrinsic ethical dimension of medicine and consequent eclipse of traditional medical ethics, currently all but assimilated by bioethics.

The Diagnostic Yield of Array Comparative Genomic Hybridization Is High Regardless of Severity of Intellectual Disability/Developmental Delay in Children.

Microarray-based comparative genomic hybridization is a method of molecular analysis that identifies chromosomal anomalies (or copy number variants) that correlate with clinical phenotypes. The aim of the present study was to apply a clinical score previously designated by de Vries to 329 patients with intellectual disability/developmental disorder (intellectual disability/developmental delay) referred to our tertiary center and to see whether the clinical factors are associated with a positive outcome of aCGH analyses. Another goal was to test the association between a positive microarray-based comparative genomic hybridization result and the severity of intellectual disability/developmental delay.

Laparoscopic versus open appendectomy in the management of acute appendicitis in children: a multicenter retrospective study.

Aim: Acute appendicitis is one of the most common indications for emergency surgery in children. Open appendectomy (OA) has been the gold standard treatment for over 100 years. In the last three decades, the introduction of minimally invasive techniques, such as laparoscopic appendectomy (LA) and transumbilical laparoscopically assisted appendectomy (TULAA), has changed the approach to the disease.

Candida pneumonia in a term infant after prolonged use of inhaled corticosteroids for bronchopulmonary dysplasia (BPD).

Candida spp. frequently cause invasive fungal disease in neonates, and many organs or apparatus can be involved through bloodstream dissemination. Though Candida spp.

Advance treatment directive: a tool for dialogue or self-protection in the physician-patient relation?

The authors intend to assess the efficacy of the advance treatment directive as a tool for involving patients into the decision-making process and the actual implementation of the physician-patient communication. It seems particularly appropriate to distinguish between "generic" advance directive, happening outside of the physician-patient relation, and documents drafted with the assistance of care providers, in the context of such an information and communication process. That is, in order to guarantee the awareness of patients and the pertinence of the disclosed indication to the current situation with reference to the subject-matter of advance treatment directive.

Retinal pigment epithelial cells promote spatial reorganization and differentiation of retina photoreceptors.

Retina differentiation involves the acquisition of a precise layered arrangement, with RPE cells in the first layer in intimate contact with photoreceptors in the second layer. Here, we developed an in vitro coculture model, to test the hypothesis that RPE cells play a pivotal role in organizing the spatial structure of the retina. We cocultured rat retinal neurons with ARPE-19 epithelial cells under various experimental conditions.

Selective outgrowth and differential tropism of amacrine and photoreceptor axons to cell targets during early development in vitro.

The axonal guidance and outgrowth in retinal neurons were investigated in cultures of pure retinal neurons (control) or in cocultures with heterologous BC3H-1 cells. Under control conditions, only about 10% of retinal neurons developed axons; coculturing with BC3H-1 cells induced early axonal outgrowth and guidance to BC3H-1 cells in most amacrine neurons. Both mechanisms were dependent on laminin and neural cell-adhesion molecules (N-CAMs) released by BC3H-1 cells, because they were prevented by antibodies directed against these molecules.

Natural interferon-beta and tamoxifen in hormone-resistant patients with advanced breast cancer.

Tamoxifen (T) is the mainstay of hormonal treatment and is able to give high response rates in selected postmenopausal women with advanced breast cancer (ABC). Nevertheless, even in responders, invariably resistance to hormones is developed. In a previous paper we reported that in a subset of patients (pts) with metastatic breast cancer the resistance to the antiestrogen could be overcome by pretreatment with natural interferon-beta (nIFN-beta) followed by the association of nIFN-beta and T.

Synthesis and inhibitory activities on platelet aggregation of some flavonoid analogues.

A series of 26 benzodioxan and benzodioxol derivatives of flavone have been prepared. The activity of the compounds on washed human platelet aggregation induced by adenosine diphosphate (ADP, 5 mumol/l), collagen (10 micrograms/ml) and calcimycin (20 mumol/l) was evaluated. The alkoxycarbonyl side chain derivatives inhibited all three types of aggregation inducers.

Thrombin induces S-D-lactoylglutathione accumulation by enhancing platelet glycolytic pathway.

1. Thrombin addition to human platelets stimulates L(+)lactate formation and S-D-lactoylglutathione (SDL) accumulation. 2.

S-D-lactoylglutathione accumulation in activated human platelets.

1. S-D-Lactoylglutathione accumulates in human platelets activated by agonists. Among the tested inducers thrombin is the most active.

Mode of action of 2-(diethylamino)-7-ethoxychromone on human platelets.

The in vitro effect of 2-(diethylamino)-7-ethoxychromone (RC39XVIII) on human platelet aggregation induced by several agonists and on thromboxane B2 formation, granule release and intracellular cAMP elevation has been studied. The chromosome-derivative exerts a dose-dependent inhibitory effect on aggregation produced by U46619, arachidonic acid, thrombin, collagen and ADP. RC39XVIII inhibits aggregation, TxB2 formation and granule release in parallel.

Antiplatelet effect of 2-(diethylamino)-7-hydroxychromone.

In this study the in vitro influence of 2-(diethylamino)-7-hydroxychromone (RC39II) on platelet aggregating responses, thromboxane A2 (TxA2) production, release reaction and intraplatelet cyclic AMP (cAMP) content has been investigated. The drug exerts a dose-dependent inhibitory effect on aggregating response to arachidonic acid, U46619, thrombin, collagen and calcium ionophore A23187. Inhibiting concentrations of RC39II also prevent platelet release reaction and TxA2 formation.

Platelets of patients affected with essential thrombocythemia are abnormal in plasma membrane and adenine nucleotide content.

The adenine nucleotides present in distinct cellular compartments of platelets of 27 patients affected with essential thrombocythemia have been measured. In order to quantify granule-bound nucleotides and adenylic cytoplasmic pool, platelets have been stimulated with thrombin or treated with increasing digitonin concentrations, respectively. Among patients, we have identified two groups: 12 patients (Group 1) had normal platelet level of ATP and ADP both in dense granules as well as in cytoplasmic pool.

Protein composition in resting and activated platelets of type I diabetic patients.

Protein composition of platelets of eleven type I diabetic patients and thirteen control subjects were analyzed by SDS polyacrylamide gel electrophoresis. Bands have been scanned and quantified. No significant difference was shown between controls and patients in any of the bands identified in electrophoretic patterns of whole platelet, membrane fraction, resting, activated and aggregated cytoskeleton.

Inhibition of the glycolytic pathway by methylglyoxal in human platelets.

The incubation of human platelets with methylglyoxal and glucose produces a rapid transformation of the ketoaldehyde to D-lactate by the glyoxalase system and a partial reduction in GSH. Glucose utilization is affected at the level of the glycolytic pathway. No effect of the ketoaldehyde on glycogenolysis and glucose oxidation through the hexose monophosphate shunt was demonstrated.

Alkaline extraction and reverse-phase high-performance liquid chromatography of adenine and pyridine nucleotides in human platelets.

The levels of adenine (ATP, ADP, AMP) and pyridine (NAD, NADH) nucleotides in human platelets have been measured by a simple and reproducible method. A rapid alkaline extraction allows a complete recovery of the compounds concerned. The metabolic ATP and ADP in the cytosolic fraction, the amount released upon thrombin stimulation, and the ADP bound to F-actin have also been evaluated.

Short-chain fatty acids produced by anaerobic bacteria alter the physiological responses of human neutrophils to chemotactic peptide.

The effect of some short-chain fatty acids (SCFA) produced by anaerobic bacteria, namely acetic, propionic, isobutyric, butyric, isovaleric and succinic acids, on production of light and release of lysozyme by human neutrophils exposed to chemotactic peptide fMet-Leu-Phe was investigated. A short period of incubation of neutrophils with SCFA led to marked inhibition of both granulocytic chemiluminescence and degranulation (P less than 0.001).