Peripheral mononuclear cell rejuvenation for senescence surveillance in Alzheimer disease.

Recent observations have pointed out that microglia, astrocytes and cerebrovascular endothelial cells senescence might contribute to the onset or progression of sporadic AD. The accumulation of senescent dysfunctional microglia or senescence related changes of other cells within CNS could be causally implicated in AD and age-related dysfunction and their efficient removal could represent a pivotal mechanism to prevent or delay neurodegeneration. The question how senescent cells are cleared from CNS has been poorly investigated, even though it is reasonable to believe that resident microglia is involved in this task.

Leptin deficiency modulates allograft survival by favoring a Th2 and a regulatory immune profile. [corrected].

Leptin, an adipose-secreted hormone, links metabolism and immunity. Our aim was to determine whether leptin affects the alloimmune response. We used an allogeneic skin transplant model as a means to analyze the allograft immune response in Lep(ob/ob) and wild-type mice.

Preclinical evaluation of non-imidazole histamine H3 receptor antagonists in comparison to atypical antipsychotics for the treatment of cognitive deficits associated with schizophrenia.

Cognitive deficits associated with schizophrenia (CDS) are implicated as a core symptom cluster of the disease and are associated with poor daily life functioning. Unfortunately, current antipsychotic agents provide little alleviation of CDS, representing a critical unmet therapeutic need. Here we investigated the effects of ABT-239 and A-431404, non-imidazole histamine H(3) receptor (H(3)R) antagonists, in animal models with relevance to CDS.

Neural and behavioral correlates of food allergy.

Food allergy accounts for a great number of reactions leading to diminished quality of life in western countries. There has been an abundance of reports of behavioral changes, as well as psychiatric conditions associated with food allergy over the past decades. Most of this field inspired little medical attention for its lack of a solid scientific ground.

Immune regulatory properties of allogeneic adipose-derived mesenchymal stem cells in the treatment of experimental autoimmune diabetes.

Adipose-derived mesenchymal stem cells (ADMSCs) display immunosuppressive properties, suggesting a promising therapeutic application in several autoimmune diseases, but their role in type 1 diabetes (T1D) remains largely unexplored. The aim of this study was to investigate the immune regulatory properties of allogeneic ADMSC therapy in T cell-mediated autoimmune diabetes in NOD mice. ADMSC treatment reversed the hyperglycemia of early-onset diabetes in 78% of diabetic NOD mice, and this effect was associated with higher serum insulin, amylin, and glucagon-like peptide 1 levels compared with untreated controls.

Survival study of metallothionein-1 transgenic mice and respective controls (C57BL/6J): influence of a zinc-enriched environment.

The role of metallothioneins (MTs) in aging is not completely understood. Several studies have shown evidence that these proteins could represent a defense system against oxidative damage, but survival studies on mice overexpressing MTs are poor. Here we describe a survival study performed on old MT-1-overexpressing mice (MT-TG) and their respective controls (C57BL/6J) fed a standard or zinc (Zn)-supplemented diet.

Synthesis and SAR studies of imidazo-[1,2-a]-pyrazine Aurora kinase inhibitors with improved off-target kinase selectivity.

The structure-activity relationships of new Aurora A/B kinase inhibitors derived from the previously identified kinase inhibitor 12 are described. Introduction of acetic acid amides onto the pyrazole of compound 12 was postulated to influence Aurora A/B selectivity and improve the profile against off-target kinases. The SAR of the acetic acid amides was explored and the effect of substitution on enzyme inhibition as well as mechanism-based cell activity was studied.

Development of a stereoselective Ugi reaction starting from an oxanorbornene β-amino acid derivative.

We have synthesised a novel oxanorbornene β-aminoacid derivative and employed it in a stereoselective Ugi reaction. Hypothesis regarding the mechanism taking place during the reaction have been made and validated through the determination of the relative and absolute configuration of the Ugi adducts. Use of the correct choice of solvents can increase stereoselection.

Comparison of synthetic oviductal fluid and G1/G2 medium under low-1 oxygen atmosphere on embryo production and pregnancy rates in Nelore (Bos indicus) cattle.

In this work, we evaluated whether embryo development and pregnancy rates would be affected by culturing bovine Bos indicus embryos in Synthetic Oviductal Fluid with amino acids (SOFaa) or G1/G2 sequential medium under a low-oxygen atmosphere. Using Ovum Pick Up, we obtained 1,538 oocytes, divided into G1/G2 (n = 783) and SOFaa (n = 755). No difference was observed for blastocyst development among the groups (27.

Assessment of glycemic control among diabetic residents in nursing homes.

We assessed hemoglobin A1c (HbA1c) among 88 diabetic residents in three Italian nursing homes, and compared figures with current guidelines and reports in the literature. Mean HbA1c was 6.5%; this paper from Southern Europe confirms recent findings in nursing homes on HbA1c values well below recommended targets.

Toxicity of the fungicide trifloxystrobin on tadpoles and its effect on fish-tadpole interaction.

Contamination of aquatic systems is a major environmental stress that can interfere with predator-prey interactions, altering prey or predator behavior differentially. We determined toxicity parameters of the fungicide trifloxystrobin (TFS) and examined its effects on predation rate, using a fish predator (Synbranchus marmoratus) and four anuran tadpole species as prey (Rhinella arenarum, Physalaemus santafecinus, Leptodactylus latrans, and Elachistocleis bicolor). TFS was not equally toxic to the four tadpole species, E.

Micronutrient (Zn, Cu, Fe)-gene interactions in ageing and inflammatory age-related diseases: implications for treatments.

In ageing, alterations in inflammatory/immune response and antioxidant capacity lead to increased susceptibility to diseases and loss of mobility and agility. Various essential micronutrients in the diet are involved in age-altered biological functions. Micronutrients (zinc, copper, iron) play a pivotal role either in maintaining and reinforcing the immune and antioxidant performances or in affecting the complex network of genes (nutrigenomic approach) involved in encoding proteins for a correct inflammatory/immune response.

[Nursing managers: study to assess the expectations of nursing coordinators in a Northern Italian Hospital].

In modern health-care , nursing managers play a strategic role in improving the quality of care and the skills of carers, since management and leadership strategies are known to be decisive in the deployment of resources and professional development. The aim of this study is to present the opinions and expectations of nursing coordinators regarding their managerial role. During the creation of a nursing service unifying the management of 3 local health authorities in Northern Italy, with different organizational and professional features, nursing coordinators were asked to fill in a questionnaire.

Diversity oriented and chemoenzymatic synthesis of densely functionalized pyrrolidines through a highly diastereoselective Ugi multicomponent reaction.

A highly diastereoselective Ugi reaction involving a chiral cyclic imine, two enantiomerically pure isocyanides and various carboxylic acids was employed for the synthesis of polyfunctionalized pyrrolidines. Both chiral substrates have been efficiently prepared by chemoenzymatic methodologies from readily available achiral substrates. This highly convergent approach can find an application in the fragment-based drug discovery process.

Regulatory T cells accumulate in the lung allergic inflammation and efficiently suppress T-cell proliferation but not Th2 cytokine production.

Foxp3(+)CD25(+)CD4(+) regulatory T cells are vital for peripheral tolerance and control of tissue inflammation. In this study, we characterized the phenotype and monitored the migration and activity of regulatory T cells present in the airways of allergic or tolerant mice after allergen challenge. To induce lung allergic inflammation, mice were sensitized twice with ovalbumin/aluminum hydroxide gel and challenged twice with intranasal ovalbumin.

Speciation of trace elements in human serum by micro anion exchange chromatography coupled with inductively coupled plasma mass spectrometry.

Speciation analysis of essential trace elements in human serum provides important information on nutritional status and homeostatic mechanisms regulating transport processes, acute phase reactions, and protection against oxidative damage. Anion exchange high-performance liquid chromatography (HPLC) combined with inductively coupled plasma mass spectrometry (ICP-MS) has proved to be a useful tool in speciation. Here we describe a fast method that can be applied to carry out the speciation of Fe, Cu, Zn, and Se in as little as 1 microl [corrected] of serum.

The influence of diet on intra and inter-individual variability of urinary excretion of arsenic species in Italian healthy individuals.

To study the effect of eating foods with a high arsenic (As) content on the intra and inter-individual variability of urinary concentrations of the As species, daily urine samples were collected for 10 consecutive days from 12 healthy male subjects. A daily food diary was kept throughout the study period. Personal exposure to airborne As was measured once during the study.

Therapy efficacy in chronic aphasia.

There is good evidence that aphasia therapy is effective if sufficiently prolonged or intensive and that chronic aphasic individuals can also benefit from therapy, but data on chronic aphasia are scanty. The aim of this retrospective study was to investigate whether chronic aphasia benefits from a very intensive therapeutic regimen. We revised the files (January 2000 to December 2008) of the chronic subjects whom we suggested have periodic sessions in our Unit (generally once a week) and 2-3 hours daily of homework with the help of a family member, supervised and controlled by the speech-therapist.

Long-range diastereoselectivity in Ugi reactions of 2-substituted dihydrobenzoxazepines.

The Ugi reaction of 2-substituted dihydrobenzoxazepines was found to proceed with unexpectedly good diastereoselectivitiy (diastereoisomeric ratios up to 9:1), despite the large distance between the pre-existing stereogenic centre and the newly generated one. This result represents the first good 1,4 asymmetric induction in an Ugi reaction as well as the first example of diastereoselective Ugi reaction of seven membered cyclic imines. It allows the diversity-oriented synthesis of various tetrahydro[f][1,4]benzoxazepines.

[Lesser validity of urinary benzene than S-phenylmercapturic acid for measuring occupational and environmental exposure to very low concentrations of benzene].

Aim: To study the validity of urinary benzene as a biomarker of low and very low exposure to this toxicant, as compared with t,t-muconic acid (t,t-MA) and S-phenylmercapturic acid (SPMA), also taking into account the influence of cigarette smoking and co-exposure to toluene on the urinary excretion of benzene.

Materials And Methods: The results obtained in two different studies were compared: in the first, workers occupationally exposed to low concentrations of benzene (18 fuel tanker drivers and 23 filling station attendants) were compared with 31 controls and in the second, workers exposed to very low concentrations of benzene (the same 23 filling station attendants) were compared with the 31 controls. Exposure to airborne benzene and toluene was monitored with passive personal samplers (Radiello).

Novel application of α-azido aldehydes in multicomponent reactions: synthesis of triazolo-fused dihydrooxazinones via a Passerini reaction-dipolar cycloaddition strategy.

α-Azido aldehydes can be employed in Passerini reactions with isocyanides and various propiolic acids to afford the three-component adducts in moderate to good yields. These compounds undergo a straightforward azide-alkyne dipolar cycloaddition to furnish triazolo-fused dihydrooxazinones.

Beyond Ugi and Passerini reactions: multicomponent approaches based on isocyanides and alkynes as an efficient tool for diversity oriented synthesis.

The reaction of isocyanides with electron deficient alkynes has been first reported in 1969, about ten years after the first reports on the famous Ugi four component reaction. However it took about thirty years to realise that the zwitterionic intermediate originating from interaction of the two species could be trapped by a third component, thus giving the start to a novel class of isocyanide-based multicomponent reactions. From that first report dated 1996 there has been an ongrowing interest that has produced, so far, about 150 distinct scientific papers.