Factors associated with circulating concentrations of irisin in the general population cohort of the ABCD study.

OBJECTIVE: Animal studies have shown that irisin is a myokine secreted following physical exercise, and that it induces the remodeling of white adipose tissue toward brown adipose tissue. Therefore, a protective role of irisin against obesity, diabetes, and other metabolic and cardiovascular conditions has been hypothesized. However, data in humans are contradictory and few data are available concerning the general population. DESIGN: We aimed to evaluate the association between serum irisin concentrations and habitual physical activity, as well as other metabolic and cardiovascular factors in a general population in a Mediterranean area. METHODS: We considered 858 consecutive individuals included in the ABCD (Alimentazione, Benessere Cardiovascolare e Diabete) study (ISRCTN15840340), a longitudinal observational single-center study of a cohort representative of the general population of Palermo, Sicily. Irisin serum concentrations (Phoenix Europe, Germany), habitual physical activity (HPA) level, and other blood and clinical variables were measured. RESULTS: The irisin serum concentrations were not normally distributed in the cohort (Shapiro-Wilk test=0.94; P<0.001). A significant association between irisin concentrations and HPA was observed (P<0.001). Irisin concentrations were higher in women than in men (P<0.01), and significantly correlated with serum concentrations of HDL-cholesterol (P<0.05) and hs-C-reactive protein (hs-CRP; P<0.05). Binary logistic regression analysis demonstrated that high (⩾ median value) irisin serum concentrations were significantly associated with female gender (OR=1.63; 95% CI=1.16-2.28), high serum hs-CRP concentrations (OR=1.61; 95% CI=1.02-2.54) and the HPA level (OR=1.42; 95% CI=1.02-1.96). CONCLUSIONS: Our study confirms, in a cohort of a general population, that irisin concentrations gradually increase with the usual level of habitual physical activity.

Tetanus vaccination, antibody persistence and decennial booster: a serosurvey of university students and at-risk workers.

The aim of the present research is to verify the immune status against tetanus in students and workers exposed to risk and to ascertain whether a decennial booster is necessary. Antibodies against tetanus were measured in 1433 workers and students of Padua University (Italy). The enrolment criterion was the ability to provide a booklet of vaccinations released by a public health office. The influence of age, gender, the number of vaccine doses, and the interval since the last dose was determined. Ten years after the last dose, the majority of subjects (95·0%) displayed an antibody titre above the protective level (⩾0·10 IU/ml), and half of these (49·1%) had a long-term protective level (⩾1·0 IU/ml). According to our data, titre depends on both the number of vaccine doses and the interval since the last dose (P < 0·0001). Five vaccine doses and an interval of at least 10 years since the last dose are predictive of a long-term protective titre in absence of a booster (1·97 IU/ml). These data suggest that when primary series are completed, a decennial booster is unnecessary for up to 20 years. Furthermore, we recommend measuring the antibody level before a new booster is given to prevent problems related to over-immunisation.

Misdiagnosis of familial Mediterranean fever in patients with Anderson-Fabry disease.

Fabry disease (FD) is an underdiagnosed pathology due to its symptomatology that overlaps with various systemic and rheumatic disorders, including familial Mediterranean fever (FMF). We examined the Mediterranean fever (MEFV) and α-galactosidase A (GLA) genes, whose mutations are responsible for FMF and FD, respectively, in 42 unrelated patients diagnosed with FMF, which revealed significant ambiguity regarding some of the symptoms which are also present in FD. The objective of this study was to determine the spectrum of mutations present in these genes, in order to identify cases of mistaken diagnosis of FMF and/or missed diagnosis of FD. Ten out of 42 patients had one mutation in homozygosis or two different mutations in heterozygosis in the MEFV gene; 20/42 had a single heterozygous mutation, and 12/42 did not have genetic alterations in MEFV. The analysis of the GLA gene conducted on all the samples revealed that three subjects, and some members of their families, had two different exonic mutations associated with FD. Family studies allowed us to identify eight other cases of FD, bringing the total undiagnosed subjects to 11/53. Analyzing the MEFV and GLA genes in patients with clinical diagnoses of FMF proved to be fundamentally important for the reduction of diagnostic errors.

Exciton-exciton annihilation in organic lanthanide complexes.

We have investigated the mechanism of exciton-exciton annihilation in organic lanthanide complexes by measuring the excitation density dependence of photoluminescence yield in neat films of a model europium chelate. The observed luminescence efficiency reduction at high excitation intensities has been attributed to the operation of the mutual annihilation of the ligand singlet excitons. The second order interaction rate constant, the exciton diffusivity, and the singlet exciton diffusion length in this material have been determined. These results were used to evaluate the role of exciton annihilation in organic light emitting diodes, lanthanide-based organic lasers, and light up-converters. Indications concerning the optimization of the performances of such devices have also been given.

Heat-Resistant Aphanizomenon flos-aquae (AFA) Extract (Klamin®) as a Functional Ingredient in Food Strategy for Prevention of Oxidative Stress.

Microalgae are generally considered an excellent source of vitamins, minerals, and bioactive molecules that make them suitable to be introduced in cosmetics, pharmaceuticals, and food industries. Aphanizomenon flos-aquae (AFA), an edible microalga, contains numerous biomolecules potentially able to prevent some pathologies including age-related disorders. With the aim to include an AFA extract (Klamin®) as a functional ingredient in baked products, we investigated if its bioactive molecules are destroyed or inactivated after standard cooking temperature. The AFA extract was exposed to heat stress (AFA-HS), and no significant decrease in pigment, polyphenol, and carotenoid content was detected by spectroscopic analysis. Thermal stability of AFA-HS extract was demonstrated by thermogravimetric analysis (TGA), and no change in the morphology of the granules of the powder was noticed by SEM microscopic observation. By Folin-Ciocalteu, ORAC, and ABTS assays, no change in the antioxidant activity and polyphenol contents was found after high-temperature exposition. When added in cell culture, solubilized AFA-HS lost neither its scavenging ability against ROS generation nor its protective role against Abeta, the main peptide involved in Alzheimer's disease. Prebiotic and antioxidant activities of AFA extract that are not lost after thermal stress were verified on E. coli bacteria. Finally, AFA-HS cookies, containing the extract as one of their ingredients, showed increased polyphenols. Here, we evaluate the possibility to use the AFA extract to produce functional food and prevent metabolic and age-related diseases.

Effects of the Aphanizomenon flos-aquae Extract (Klamin®) on a Neurodegeneration Cellular Model.

Cyanobacteria have been recognized as a source of bioactive molecules to be employed in nutraceuticals, pharmaceuticals, and functional foods. An extract of Aphanizomenon flos-aquae (AFA), commercialized as Klamin®, was subjected to chemical analysis to determine its compounds. The AFA extract Klamin® resulted to be nontoxic, also at high doses, when administered onto LAN5 neuronal cells. Its scavenging properties against ROS generation were evaluated by using DCFH-DA assay, and its mitochondrial protective role was determined by JC-1 and MitoSOX assays. Klamin® exerts a protective role against beta amyloid- (Aß-) induced toxicity and against oxidative stress. Anti-inflammatory properties were demonstrated by NFßB nuclear localization and activation of IL-6 and IL-1ß inflammatory cytokines through ELISA. Finally, by using thioflavin T (ThT) and fluorimetric measures, we found that Klamin® interferes with Aß aggregation kinetics, supporting the formation of smaller and nontoxic structures compared to toxic Aß aggregates alone. Altogether, these data indicate that the AFA extract may play a protective role against mechanisms leading to neurodegeneration.

Angiotensin II type II receptors and colonic dysmotility in 2,4-dinitrofluorobenzenesulfonic acid-induced colitis in rats.

BACKGROUND: Angiotensin II (Ang II), the main peptide of the renin-angiotensin system (RAS), has been suggested to be involved in inflammatory bowel diseases. Since RAS has emerged as gut motility regulator, and dysmotility is associated with intestinal inflammation, our objective was to investigate in rat 2,4-dinitrobenzenesulfonic acid (DNBS)-induced colitis the functionality of RAS and its contribution to colonic motor alterations. METHODS: The effects of Ang II on the longitudinal colonic muscular contractility of control and DNBS-treated rats were characterized in vitro. Transcripts encoding for Ang II receptors were investigated by RT-PCR. KEY RESULTS: Inflamed preparations showed a longitudinal muscle marked hypocontractility. Angiotensin II caused contractile effects in both preparations, but the responses in DNBS preparations were reduced compared to controls. In both preparations, Losartan, AT1 receptor antagonist, reduced Ang II effects. PD123319, AT2 receptor antagonist, enhanced Ang II responses only in DNBS rats, as well as Nω -Nitro-L-arginine (L-NNA), nitric oxide (NO) synthase inhibitor, or tetrodotoxin (TTX), neural toxin. The co-administration of PD123319 and TTX or L-NNA produced no additive effects. PD123319 per se improved colonic contractility in inflamed tissues. The effect was reduced in the presence of L-NNA or TTX. All Ang II receptor subtypes were expressed in both preparations. CONCLUSIONS & INFERENCES: AT1 receptors mediate Ang II contractile responses in rat colon. During inflammation a recruitment of Ang II AT2 receptors would counteract AT1 -contractile activity. A tonic activation of AT2 receptors would contribute to the general reduction in muscle contractility during experimental inflammation. A role for enteric neurons and NO is also suggested.

[Hypothesis of the correlation of personality characteristics and the clinical history of bronchogenic cancer]. / Ipotesi di correlazione tra caratteristiche di personalità e storia clinica del cancro broncogeno.

A correlation between the personality profile and the clinical history in lung cancer patients was studied. Selection of cases included in the sample only surgical patients with a medium educational level and a tested capability to understand a specific questionnaire. One hundred and seventy patients were selected and the so-called C.R.I.C.S. (Clinical-Rated Inventory of Character Style) was applied. Score variations were recorded after curative resection as well as during relapse. Changes in the character profile pattern were found in all subjects who experienced the disease and its surgical treatment. These changes occurred either in "regression"-with an increase of schizoid, narcissistic or hysterical aspects-or in a "positive evolution", with a decrease of paranoid traits and into a depressive position. The two groups of responses demonstrated a similar percentage.

[Acute alithiasic cholecystitis (pathogenetic and clinical considerations)]. / Le colecistiti acute alitiasiche (considerazioni patogenetiche e cliniche).

The authors address the topic of acute acalculous cholecystitis and examine the related aetiopathogenetic and clinical problems, taking as their starting point two cases of the disease observed in their department.

[Hemoperitoneum secondary to aneurysm of the pancreatico-duodenal artery: report of a clinical case]. / Emoperitoneo da rottura di un aneurisma dell'arteria pancreatico--duodenale: a proposito di un caso clinico.

Pancreaticoduodenal artery (PD A) aneurysms are rare, with a reported incidence of 2% among all splanchnic artery aneurysms. Most of these lesions are undetectable until symptoms of rupture occur. In similar cases (65%), PDA rupture is usually associated with a high mortality rate, with fatal bleeding into the retroperitoneal space, intraperitoneal cavity or gastrointestinal tract. Clinical picture without rupture also has been reported (35%) and is often associated with atypic abdominal signs and symptoms or diagnosed incidentally on radiology studies. The Authors report a case of octogenarian patient with ruptured PDA aneurysm and bleeding into the retroperitoneal space presenting with stable clinical condition. Surgical treatment was performed successfully after radiological diagnosis of retroperitoneal haematoma with good outcome. Patients presenting catastrophic clinical condition need rapid resuscitation and emergency laparotomy: control of the bleeding site may be successful and aetiologycal diagnosis delayed after perioperative angiography. Further laparotomy is mandatory for a definitive treatment such as PDA obliteration or resection. An alternative therapy is the transcatheter embolization. In patients with relatively stable condition, radiological study is stressed. Anyway, the aneurysm should be obliterated whenever possible to avoid rebleeding or local complications such as erosion of the neighboring structure. In conclusion, an appropriate and early treatment lead to a good outcomes.

[Diagnosis of thoraco-pulmonary disorders: role of videothoracoscopy]. / Diagnostica delle affezioni toraco-polmonari: ruolo della VTS.

Videothoracoscopy can be used for diagnostic purposes when the other non-invasive methods are not satisfactory for an accurate histological diagnosis in lung and pleural pathology. The role of VTS was confirmed in the cases, observed from 1993 and surgically treated, which are herein discussed.

Curcumin induces apoptosis in human neuroblastoma cells via inhibition of AKT and Foxo3a nuclear translocation.

Neuroblastoma (NB) is one of the most frequent extracranial solid tumors in children. It accounts for 8-10% of all childhood cancer deaths, and there is a need for development of new drugs for its treatment. Curcumin (diferuloylmethane), a major active component of turmeric (Curcuma longa), has been shown to exert anti-tumor activity on NB, but the specific mechanism by which curcumin inhibits cancer cells proliferation remains unclear. In the present study, we investigated the anti-proliferative effect of curcumin in human LAN5 NB cells. Curcumin treatment causes a rapid increase in reactive oxygen species and a decrease in the mitochondrial membrane potential-events leading to apoptosis activation. Furthermore, curcumin induces decrease in haet shock protein (Hsp)60 and hexokinase II mitochondrial protein levels and increase in the pro-apoptotic protein, bcl-2 associated death promoter (BAD). Moreover, we demonstrate that curcumin modulates anti-tumor activity through modulation of phosphatase and tensin homolog deleted on chromosome 10 and consequential inhibition of the survival Akt cell-signaling pathway. Inhibition of Akt causes its translocation into the cytoplasm and import of Foxo3a into the nucleus where it activates the expression of p27, Bim, and Fas-L pro-apoptotic genes. Together, these results take evidence for considering curcumin as a potential therapeutic agent for patients with NB.

Clinical utility of preoperative screening with STOP-Bang questionnaire in elective surgery.

BACKGROUND: Obstructive sleep apnea (OSA) is a common disease which increases the risk of perioperative complications. The aim of this study is to assess the clinical utility of preoperative screening for OSA in determining the prevalence of patients at high risk of OSA in a surgical population, the incidence of difficult airway management and the incidence of perioperative complications. METHODS: We conducted a multisite, prospective observational study on adult patients scheduled for elective surgery. All patients completed a STOP-Bang questionnaire as a part of their preoperative evaluation. Collected data included: demographic data, type of surgery, ASA class, postoperative course, complications within 48 hours, difficult intubation (DI) and difficult mask ventilation (DMV) rates. RESULTS: A total of 3452 consecutive patients were recruited; 2997 (87%) were identified as low OSA risk patients and 455 (13%) were identified as high OSA risk patients; 113 (3%) postoperative complications, 315 (9%) cases of DMV and 375 (11%) of DI were observed. The percentage of postoperative complications in patients with HR-OSA was 9%, while the percentage of DI was 20% and the percentage of DMV was 23%. High risk for OSA and higher BMI (≥30 Kg m-2) were independently associated with risk for perioperative complications. CONCLUSION: In conclusion, this study demonstrates that the prevalence of high OSA risk patients in the surgical population is high. The increase in the rates of perioperative complications justifies the implementation of perioperative strategies that use the STOP-Bang as a tool for triage.

[Storage at room temperature does not change cisatracurium onset time: a prospective, randomized, double-blind controlled study]. / La température de conservation du cisatracurium ne modifie pas le délai d'action: étude randomisée, en double insu

OBJECTIVE: Storage of cisatracurium at room temperature seems to have no effect on its degradation in vitro contrary to the recommendations of storage at +4°C. The purpose of this study was to evaluate the influence of cisatracurium' s storage temperature on its onset time. STUDY DESIGN: Prospective, randomized, double-blind trial study. PATIENTS AND METHODS: Thirty patients were enrolled. The control group consisted of 15 patients receiving cisatracurium (0.15mg/kg) stored at room temperature and the intervention consisted of 15 patients receiving cisatracurium (0.15mg/kg) stored at +4°C. The primary endpoint was to compare cisatracurium onset time depending on the storage temperature. RESULTS: Cisatracurium onset time was 235 (180-292) seconds in the "room temperature" group vs. 240 (210-292) seconds in the "refrigerated" group. There was no difference between the onset of cisatracurium depending on the temperature of storage (p=0.51). Subgroups analysis in the "room temperature" group did not show any difference in cisatracurium onset depending on whether it was stored at room temperature for one, two or three weeks. Excellent intubation score was obtained for 100% of the patients. CONCLUSION: This study demonstrated that cisatracurium's storage at room temperature had no influence on its onset time. It provides an argument for the preservation of cisatracurium at room temperature for a period not exceeding 21 days. Monitoring the onset of curarization may increase the quality score of intubation.

Age-related inflammation: the contribution of different organs, tissues and systems. How to face it for therapeutic approaches.

A typical feature of ageing is a chronic, low-grade inflammation characterized by a general increase in the production of pro-inflammatory cytokines and inflammatory markers ("inflamm-ageing"). This status may slowly damage one or several organs, especially when unfavorable genetic polymorphisms and epigenetic alterations are concomitant, leading to an increased risk of frailty together with the onset of age-related chronic diseases. The contribution of different tissues (adipose tissue, muscle), organs (brain, liver), immune system and ecosystems (gut microbiota) to age-related inflammation ("inflamm-ageing") will be discussed in this review in the context of its onset/progression leading to site-restricted and systemic effects. Moreover, some of the possible strategies and therapies to counteract the different sources of molecular mediators which lead to the age-related inflammatory phenotype will be presented.

Immune-inflammatory responses and oxidative stress in Alzheimer's disease: therapeutic implications.

Alzheimer's disease (AD) is a heterogeneous and progressive neurodegenerative disease which in Western society mainly accounts for clinical dementia. AD has been linked to inflammation and oxidative stress. Neuro-pathological hallmarks are senile plaques, resulting from the accumulation of several proteins and an inflammatory reaction around deposits of amyloid, a fibrillar protein, Abeta, product of cleavage of a much larger protein, the beta-amyloid precursor protein (APP) and neurofibrillary tangles. Inflammation clearly occurs in pathologically vulnerable regions of AD and several inflammatory factors influencing AD development, i.e. environmental factors (pro-inflammatory phenotype) and/or genetic factors (pro-inflammatory genotype) have been described. Irrespective of the source and mechanisms that lead to the generation of reactive oxygen species, mammalian cells have developed highly regulated inducible defence systems, whose cytoprotective functions are essential in terms of cell survival. When appropriately activated, each one of these systems has the possibility to restore cellular homeostasis and rebalance redox equilibrium. Increasing evidence, support the notion that reduction of cellular expression and activity of antioxidant proteins and consequent augment of oxidative stress are fundamental causes for ageing processes and neurodegenerative diseases., including AD. The better understanding of different molecular and cellular inflammatory mechanisms is crucial for complete knowledge of AD pathophysiology, hence for its prevention and drug therapy. Accordingly, two lines of preventive therapeutics can be outlined, the first based on anti-inflammatory drugs, the second one on anti-oxidative properties.