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Using information and communication technologies, it is applied the conceptual framework of Teaching to understand an e-learning chemistry course , at the Faculty of Engineering, La Plata National University. It was designed a didactic sequence centered on understanding. It was taken the topic of "alternative energies" as thread , considering the concept of chemical reaction as a central generative topic. The teaching sequence starts from a schematic image showing the process of obtaining energy through alternative sources and was accompanied by questions, they are answered by students in individual blogs. The research process with guided tutorial is done in the discussion forums on-line, up to the synthesis stage, where the final answers in the blogs reflects the level of understanding achieved. The aim to improve the performance of understanding was reached by almost all the students.

We performed comprehensive structure-activity relationship (SAR) studies on the peptide portion of antiproliferative factor (APF), a sialylated frizzled-8 related glycopeptide that inhibits normal bladder epithelial and urothelial carcinoma cell proliferation. Glycopeptide derivatives were synthesized by solid-phase methods using standard Fmoc chemistry and purified by RP-HPLC; all intermediate and final products were verified by HPLC-MS and NMR analyses. Antiproliferative activity of each derivative was determined by inhibition of (3)H-thymidine incorporation in primary normal human bladder epithelial cells. Structural components of the peptide segment of APF that proved to be important for biological activity included the presence of at least eight of the nine N-terminal amino acids, a negative charge in the C-terminal amino acid, a free amino group at the N-terminus, maintenance of a specific amino acid sequence in the C-terminal tail, and trans conformation for the peptide bonds. These data provide critical guidelines for optimization of structure in design of APF analogues as potential therapeutic agents.

Runx1 participation in epithelial mammary cells is still under review. Emerging data indicates that Runx1 could be relevant for breast tumor promotion. However, to date no studies have specifically evaluated the functional contribution of Runx1 to control gene expression in mammary epithelial tumor cells. It has been described that Runx1 activity is defined by protein context interaction. Interestingly, Foxp3 is a breast tumor suppressor gene. Here we show that endogenous Runx1 and Foxp3 physically interact in normal mammary cells and this interaction blocks Runx1 transcriptional activity. Furthermore we demonstrate that Runx1 is able to bind to R-spondin 3 (RSPO3) and Gap Junction protein Alpha 1 (GJA1) promoters. This binding upregulates Rspo3 oncogene expression and downregulates GJA1 tumor suppressor gene expression in a Foxp3-dependent manner. Moreover, reduced Runx1 transcriptional activity decreases tumor cell migration properties. Collectively, these data provide evidence of a new mechanism for breast tumor gene expression regulation, in which Runx1 and Foxp3 physically interact to control mammary epithelial cell gene expression fate. Our work suggests for the first time that Runx1 could be involved in breast tumor progression depending on Foxp3 availability. Fil: Recouvreux, Sol. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Grasso, Esteban Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina Fil: Echeverria, Pablo Christian. Universidad de Ginebra; Suiza. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Rocha Viegas, Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina Fil: Castilla, Lucio Hernán. University Of Massachussets. Medical School; Estados Unidos Fil: Schere Levy, Carolina Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina Fil: Tocci, Johanna Melisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina Fil: Kordon, Edith Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina Fil: Rubinstein, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina

Antiproliferative factor (APF) is a low molecular weight sialoglycopeptide that is secreted by bladder cells from interstitial cystitis patients and is a potent inhibitor of both normal bladder epithelial and bladder carcinoma cell proliferation. We hypothesized that APF may produce its antiproliferative effects by binding to a transmembrane receptor. This study demonstrates that cytoskeleton-associated protein 4/p63 (CKAP4/p63), a type II transmembrane receptor, binds with high affinity to APF. The antiproliferative activity of APF is effectively inhibited by preincubation with anti-CKAP4/p63-specific antibodies, as well as by short interfering RNA knockdown of CKAP4/p63. Immunofluorescent confocal microscopy showed co-localization of anti-CKAP4/p63 and rhodamine-labeled synthetic APF binding in both cell membrane and perinuclear areas. APF also inhibits the proliferation of HeLa cervical carcinoma cells that are known to express CKAP4/p63. These data indicate that CKAP4/p63 is an important epithelial cell receptor for APF.

This review article focuses primarily on the work carried in our laboratories over the last few years using luminescent and colorimetric sensors, where the anion recognition occurs through hydrogen bonding in organic or aqueous solvents. This review begins with the story of the discovery of fluorescent photoinduced electron transfer (PET) sensors for anions using charged neutral urea or thiourea receptors where both fluorescent and NMR spectroscopic methods monitored anion recognition. This work led to the development of dual luminescent and colorimetric anion sensors based on the use of the ICT based naphthalimide chromophore, where ions such as fluoride gave rise to changes in both the fluorescence and the absorption spectra of the sensors, but at different concentrations. Here, the former changes were due to hydrogen bonding interactions, whereas the latter was due to the deprotonation of acidic protons, giving rise to the formation of the bifluoride anion (HF2−). Modification of the 4-amino-l,8-naphthalimide moiety has facilitated the formation of colorimetric anion sensors that work both in organic or aqueous solutions. Such charge neutral receptor motifs have also been incorporated into organic scaffolds with norbomyl and calixarene backbones, which have enabled us to produce anion directed self-assembled structures.

The development of functional 1,8-naphthalimide derivatives as DNA targeting, anticancer and cellular imaging agents is a fast growing area and has resulted in several such derivatives entering into clinical trials. This review gives an overview of the many discoveries and the progression of the use of 1,8-naphthalimides as such agents and their applications to date; focusing mainly on mono-, bis-naphthalimide based structures, and their various derivatives (e.g. amines, polyamine conjugates, heterocyclic, oligonucleotide and peptide based, and those based on metal complexes). Their cytotoxicity, mode of action and cell-selectivity are discussed and compared. The rich photophysical properties of the naphthalimides (which are highly dependent on the nature and the substitution pattern of the aryl ring) make them prime candidates as probes as the changes in spectroscopic properties such as absorption, dichroism, and fluorescence can all be used to monitor their binding to biomolecules. This also makes them useful species for monitoring their uptake and location within cells without the use of co-staining. The photochemical properties of the compounds have also been exploited, for example, for photocleavage of nucleic acids and for the destruction of tumour cells.

The development of functional 1,8-naphthalimide derivatives as DNA targeting, anticancer and cellular imaging agents is a fast growing area and has resulted in several such derivatives entering into clinical trials. This review gives an overview of the many discoveries and the progression of the use of 1,8-naphthalimides as such agents and their applications to date; focusing mainly on mono-, bis-naphthalimide based structures, and their various derivatives (e.g. amines, polyamine conjugates, heterocyclic, oligonucleotide and peptide based, and those based on metal complexes). Their cytotoxicity, mode of action and cell-selectivity are discussed and compared. The rich photophysical properties of the naphthalimides (which are highly dependent on the nature and the substitution pattern of the aryl ring) make them prime candidates as probes as the changes in spectroscopic properties such as absorption, dichroism, and fluorescence can all be used to monitor their binding to biomolecules. This also makes them useful species for monitoring their uptake and location within cells without the use of co-staining. The photochemical properties of the compounds have also been exploited, for example, for photocleavage of nucleic acids and for the destruction of tumour cells.

Antiproliferative factor (APF), a sialylated glycopeptide secreted by explanted bladder epithelial cells from interstitial cystitis/painful bladder syndrome (IC/PBS) patients, and its unsialylated analogue (as-APF) significantly decrease proliferation of bladder epithelial cells and/or certain carcinoma cell lines in vitro. We recently reported a structure-activity relationship profile for the peptide portion of as-APF and revealed that truncation of the C-terminal alanine did not significantly affect antiproliferative activity. To better understand the structural basis for the maintenance of activity of this truncated eight amino acid as-APF (as-APF8), we synthesized several amino acid-substituted derivatives and studied their ability to inhibit bladder epithelial cell proliferation in vitro as well as their solution conformations by CD and NMR spectroscopy. While single amino acid changes to as-APF8 often strongly reduced activity, full potency was retained when the trivaline tail was replaced with three alanines. The Ala(6-8) derivative 9 is the simplest, fully potent APF analogue synthesized to date.

SR58611A is a selective beta(3)-adrenoceptor (Adrb3) agonist which has demonstrated antidepressant and anxiolytic properties in rodents. The present study confirmed the detection of Adrb3 mRNA transcript in rodent brain sub-regions and evaluated the effect of SR58611A on serotonergic and noradrenergic transmission in rats and mice in an attempt to elucidate the mechanism(s) underlying these properties. SR58611A (3 and 10 mg/kg, p.o.) increased the synthesis of 5-HT and tryptophan (Trp) levels in several rodent brain areas (cortex, hippocampus, hypothalamus, striatum). Moreover, SR58611A (10 mg/kg, p.o.) increased the release of 5-HT assessed by in vivo microdialysis in rat prefrontal cortex. Systemic (3 mg/kg, i.v.) or chronic administration of SR58611A (10 mg/kg, p.o.), in contrast to fluoxetine (15 mg/kg, p.o.), did not modify the activity of serotonergic neurons in the rat dorsal raphe nucleus. The increase in 5-HT synthesis induced by SR58611A was not observed in Adrb3s knockout mice, suggesting a selective involvement of Adrb3s in this effect. SR58611A (3 and 10 mg/kg, p.o.) did not modify norepinephrine synthesis and metabolism but increased its release in rat brain. Repeated administration of SR58611A (10 mg/kg, p.o.) did not modify basal norepinephrine release in rat prefrontal cortex whereas it prevented its tail-pinch stress-induced enhancement similarly to reboxetine (15 mg/kg, p.o.). Finally SR58611A increased the firing rate of noradrenergic neurons in the rat locus coeruleus following systemic (3 mg/kg, i.v.) or local (0.01 and 1 microM) but not chronic (10 mg/kg, p.o.) administration. These results suggest that the anxiolytic- and antidepressant-like activities of SR58611A involve an increase of brain serotonergic and noradrenergic neurotransmissions, triggered by activation of Adrb3s.

The reduction mechanism of the bronze Li(1.2)V3O8 in nonaqueous Li cells has been elucidated. Upon Li(+) insertion, a solid solution is formed with an upper composition of Li(approximately 3)V3O8. Within this composition range, Li(+) progressively fills the tetrahedral sites available in the unit cell. Four such sites are supposed to be filled at the upper composition limit. Beyond this, a new phase is nucleated to accommodate excess Li(+), this resulting in a constant cell's OCV. Li(+) insertions not greater than 3.0 eq/mol are reversible, as shown by the cycling behavior and the X-ray paterns. Owing to the outstanding structure stability and to the high speed of Li(+) diffusion in Li(1.2)V3O8, extended cycling at high rates is achievable with cells based on this bronze. 445 cycles at discharge rates variable in the range of 2-10 mA/sq cm have been obtained. 13 references.

With the aim of optimizing the performance of Li/Li1+xV3O8 cells, several aspects of cathode preparation have been examined. The influence of synthesis technique, nature and amount of conductive additives, compacting pressure, cathode loading, and particle size, has been investigated. Furthermore, the role played by the solutions on cathode efficiency has been outlined. The formulations which perform best are based on small-sized particles blended with about 20% acetylene black and compacted at very high pressures to improve the contact between particles. Such cathodes can provide high capacities at high rates and good cycling efficiencies. The kinetic loss of capacity, observed during the first few cycles, may be alleviated by choosing solutions with high fluidity and conductivity.

The enthalpies of Li + insertion into two V oxides of interest as cathodes for secondary Li batteries, i.e. V 6 O 13 and Li 1+ x V 3 O 8 have been directly measured by solution calorimetry. By comparing the integral molar enthalpies Δ H 0 / x with the corresponding Δ G 0 / x values, Δ S 0 / x higher than expected have been found for Li 1+ x V 3 O 8 . This has been correlated to a reorganization of its distorted structure induced by the initial Li + insertion. Two other cathode materials, having the same variation of the potential with Li + content, i.e. MoO 3 and (Mo 0.3 V 0.7 ) 2 O 5 , show even higher Δ S 0 / x values. The entropic values stemming from structural reorganizations add to the configurational entropies of inserted ions in determining the initial profile of E as a function of Li + .

A calorimetric study of the ionization process of 2,5-dihydroxybenzoic acid, in water—DMSO mixtures, ranging from pure water up to 0.8 mole fraction is presented. This compound shows a very different behaviour with respect to the 2,3-dihydroxy derivative because of the two hydroxyl groups which, in the relative para position, stabilize and delocalize the charge on the anion. For this reason, 2,5-(OH) 2 PhCOOH is, with the exception of 2,6-(OH) 2 PhCOOH, the strongest acid in an acidity scale of dihydroxy derivatives.

A calorimetric study of six α-amino acids is presented. These form three couples which belong to three different classes of α-amino acids. Different values of the ionization enthalpy can be related to the structure variation of the R substituent group. A sharp difference was found between hydrophobic and hydrophilic R groups.

Nonylbenzo-hexaquinone, an insoluble polymer of high theoretical specific capacity (0.489 A h/g), has been used as the cathode material in organic electrolytes instead of benzoquinone and its derivatives. The reduction mechanism is rather complex and involves two main steps, the first of which, as shown by cyclic voltammetry, is, in turn, a multi-process step. It corresponds to the uptake of 6 Li+/molecule or 0.234 A h/g. The second step tends to merge with electrolyte reduction, thus preventing a correct estimate of the total number of Li+ involved. The first reduction step is partly reversible (2.0–2.5 e− out of 6), whereas the second is irreversible. 150 cycles were obtained when cycling was performed between 2.0 and 3.5 V at 0.5 mA/cm2. A typical energy density during cycling was 127 W h/kg (electrodes only, additives included).

γ-Aminobutyric acid was found in the kidney and in some other tissues in six children. The material obtained was characterized by chromatography on cation exchange columns and on thin layer chromatography, by electrophoresis, and by the synthesis of the trimethylamino derivative, the chromatographic and electrophoretic behavior, melting point, and crystal structure of the AuCl3 salt of which were identical with those of the derivative synthesized from authentic γ-aminobutyric acid. It is concluded that in man, unlike the animals reported, γ-aminobutyric acid is not a unique constituent of the central nervous system.

The daily para-hydroxyphenylacetic acid (p-HPAA) excretion was examined in four adults under varying dietary intake. The diet varied considerably in the content of precursor amino acid, tyrosine and other phenolic acids. When the subjects were on a complete fast but for water, the total volume of urine almost doubled, the creatinine excretion doubled but the p-HPAA excretion remained approximately the same for each individual. These experiments indicate that the daily excretion of p-HPAA may be independent of dietary intake and rather constant from one day to the next in individuals. Differences occur between individuals in the daily excretion of p-HPAA while receiving the same diet, but they are within a relatively narrow range. The 24-h excretion of p-HPAA was examined in 53 people of all ages. The p-HPAA excretion begins to increase around the age of puberty. However, there were several children and adults in the study who excreted no detectable amount of p-HPAA. Tyrosine loads were given to 2 people and the urinary p-HPAA was determined over several hours. While only a small percentage of the fed tyrosine was converted to p-HPAA it is apparently a large contributor to this pool.

Following a preliminary investigation, Li/Li1+xV3O8 cells have been examined. Using samples of low x content, up to 3 eq Li+ could be accepted both chemically and electrochemically by one mole of active material. Li+ is accomodated in the tetrahedral sites existing between the (V3O8)(1+x)- layers. Li+ jumping from site to site is fast and permits high rate capabilities: at 10 mA/cm2, 1.1 eq Li+ per mole could still be inserted. The structure does not show irreversible alterations upon extended lithiation, allowing long cycle lives to be achieved. Kinetic constraints limit the recovery of the full capacity of the first discharge at medium-high rates, but the second-discharge capacity declines slowly with cycle number.

The proteins of the human body are in a constant state of flux with some proteins being synthesized and catabolized continually. Dietary proteins and tissue protein breakdown products provide a pool of amino acids which provide the building blocks for formation of new protein for growth and for rebuilding tissue protein. Essential amino acids are those not synthesized by man or not produced sufficiently rapidly enough to support this activity. Therefore, man requires a source of nitrogen and essential amino acids to support growth, protein synthesis and biosynthesis of important nitrogenous metabolites. The differences in value of food proteins are due to variations in amino acid pattern of each protein. Since the body can form only some of the amino acids, nine “essential” ones must be supplied in the diet (Table I) (McLaughlan et al., 1963, Schelling, 1975). Protein normally is not absorbed by the human intestine, but its hydrolysis products peptides and free amino acids are readily absorbed by the small intestine and transported via the portal blood. A diet low in protein or food protein which is deficient in one or more essential amino acids will restrict protein synthesis. Nonessential amino acids are generally metabolized to pyruvate which leads to gluconeogensis. Therefore, in times of great need (starvation) body proteins can provide energy via glucose. The problem here is that the conversion of protein to glucose is only about 50% efficient (Bessman, 1975) so that 100 g of glucose will require 200 g of protein or the equivalent of 1 kg of lean body weight. Most of the essential amino acids are converted to acetyl CoA and their nitrogen as well as that of the amino acids converted to glucose is lost to the body primarily as ammonia.

— The photodynamically-induced liberation of lysosomal enzymes using s-galactosidase as marker for the lysosomal enzymes has been studied by microspectrofluorometry on mouse L cells. Similar studies have been carried out using N-acetyl-s-D-glucosaminidase as marker for the lysosomal enzymes of human fibroblasts. The high sensitivity of the fluorescence detection makes it possible to use 4-methylumbelliferyl substrates for the enzymes contained in a single cell. Methylene blue and hematoporphyrin readily incorporate into both cells and upon excitation, sensitize lysosomal membrane damages, leading to enzyme release accompanying strong morphological changes.

Serial analyses of sweat NaCl concentrations by iontophoresis in children with cystic fibrosis (CF) commonly show unexplained fluctuations. Some children with previously normal values subsequently develop elevated levels. Some allergic children have values in the high normal range during acute respiratory or gastrointestinal infections and these levels decrease upon recovery. We have measured serially sweat NaCl levels in 22 children with chronic intestinal problems and/or chronic pulmonary disease who had had sweat Cl− concentrations greater than 60 mEq/L. Tests were done before and after periods of 2-13 days on an elemental diet, Vivonex, 1800-2400 cal/day with 2-3 gm Nad/day, and after varying periods on diets excluding foods to which children are commonly sensitive. Daily NaCl intake was kept in a similar range on all diets. Seven of 22 had a striking decrease in sweat Cl− to normal (range 13-60 mEq/L) on one or more diets. (The one patient with a low value of 60 mEq/L had levels on other diets over 100 mEq/L.) Three of these had initial values of 80, 84 and 85 mEq/L. In 4 patients normal concentrations persisted weeks to months while on a limited diet. Four of the 7 were shown by complement (C3) alteration following food challenges to be sensitive to foods. These results support the concept that all children with elevated sweat Cl− levels do not have CF and suggest that sweat NaCl concentrations may be a function of diet composition even when salt intake is kept constant.

Circulating amino acid levels were measured in 5 juvenile diabetics and 4 controls one hour before and one hour after breakfast and lunch. All subjects were maintained on identical diets in a clinical research center prior to and during the testing. All diabetic subjects were treated with NPH insulin on one day and regular insulin on another. Taken as a group, the diabetics were not different from the controls except for a lower alanine content in the blood. This was true whether they were taking NPH or regular insulin treatment and regardless of the fed or fasted state. However, striking differences were noted within the diabetic group. Two of the 5 diabetic subjects exhibited very high glycine levels, high serine levels and low levels of alanine, valine, leucine and isoleucine. The other three exhibited low threonine, alanine and methionine levels. In all cases the differences were significant at the 0.01 level. There were no significant differences in the glucose levels of the two groups. The amino acid differences persisted even on the days when normal pre and post prandial blood glucoses were achieved with regular insulin treatment. The data indicate that differences in the circulating amino acids of juvenile diabetics do exist. Whether these differences are due to homeostatic control of the disease or whether they are due to fundamental sub-group differences in substrate utilization or absorption remains to be proven.

The latest European Guidelines of Arterial Hypertension have officially introduced uric acid evaluation among the cardiovascular risk factors that should be evaluated in order to stratify patient's risk. In fact, it has been extensively evaluated and demonstrated to be an independent predictor not only of all-cause and cardiovascular mortality, but also of myocardial infraction, stroke and heart failure. Despite the large number of studies on this topic, an important open question that still need to be answered is the identification of a cardiovascular uric acid cut-off value. The actual hyperuricemia cut-off (> 6 mg/dL in women and 7 mg/dL in men) is principally based on the saturation point of uric acid but previous evidence suggests that the negative impact of cardiovascular system could occur also at lower levels. In this context, the Working Group on uric acid and CV risk of the Italian Society of Hypertension has designed the Uric acid Right for heArt Health project. The primary objective of this project is to define the level of uricemia above which the independent risk of CV disease may increase in a significantly manner. In this review we will summarize the first results obtained and describe the further planned analysis.

The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension conceived and designed an ad hoc study aimed at searching for prognostic cut-off values of serum uric acid (SUA) in predicting combined (fatal and non-fatal) cerebrovascular (CBV) events in the whole database. The URic acid Right for heArt Health study is a nationwide, multicenter, observational cohort study involving data on subjects aged 18-95 years recruited on a regional community basis from all the territory of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 120.7 ± 61.8 months. A total of 14,588 subjects were included in the analysis. A prognostic cut-off value of SUA able to discriminate combined CBV events (>4.79 mg/dL or >284.91 µmol/L) was identified by means of receiver operating characteristic curve in the whole database. Multivariate Cox regression analysis adjusted for confounders (age, sex, arterial hypertension, diabetes, chronic kidney disease, smoking habit, ethanol intake, body mass index, low-density lipoprotein cholesterol, and use of diuretics) identified an independent association between SUA and combined CBV events in the whole database (HR 1.249, 95% confidence interval, 1.041-1.497, p = 0.016). The results of the present study confirm that SUA is an independent risk marker for CBV events after adjusting for potential confounding variables, including arterial hypertension, and demonstrate that >4.79 mg/dL is a valid prognostic cut-off value.

Introduction Serum uric acid (SUA) has been depicted as a contributory causal factor in metabolic syndrome (MS), which in turn, portends unfavourable prognosis. Aim We assessed the prognostic role of SUA in patients with and without MS. Methods We used data from the multicentre Uric Acid Right for Heart Health study and considered cardiovascular mortality (CVM) as death due to fatal myocardial infarction, stroke, sudden cardiac death, or heart failure. Results A total of 9589 subjects (median age 58.5 years, 45% males) were included in the analysis, and 5100 (53%) patients had a final diagnosis of MS. After a median follow-up of 142 months, we observed 558 events. Using a previously validated cardiovascular SUA cut-off to predict CVM (> 5.1 mg/dL in women and 5.6 mg/dL in men), elevated SUA levels were significantly associated to a worse outcome in patients with and without MS (all p p = 0.004). Cox regression analyses identified an independent association between SUA and CVM (Hazard Ratio: 1.79 [95% CI, 1.15–2.79]; p p Conclusion Increasing SUA levels are associated with a higher CVM risk irrespective of the presence of MS: a cardiovascular SUA threshold may improve risk stratification. Graphic abstract

Aims Whether the association between uric acid (UA) and cardiovascular disease is influenced by some facilitating factors is unclear. The aim of this study was to investigate whether the risk of cardiovascular mortality (CVM) associated with elevated UA was modulated by the level of resting heart rate (HR). Methods and results Multivariable Cox analyses were made in 19 128 participants from the multicentre Uric acid Right for heArt Health study. During a median follow-up of 11.2 years, there were 1381 cases of CVM. In multivariable Cox models both UA and HR, either considered as continuous or categorical variables were independent predictors of CVM both improving risk discrimination (P ≤ 0.003) and reclassification (P Conclusion This data suggest that the contribution of UA to determining CVM is modulated by the level of HR supporting the hypothesis that activation of the sympathetic nervous system facilitates the action of UA as a cardiovascular risk factor.

Supplemental Digital Content is available in the text, Objective: The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension conceived and designed an ad-hoc study aimed at searching for prognostic cut-off values of serum uric acid (SUA) in predicting fatal myocardial infaction (MI) in women and men. Methods: The URic acid Right for heArt Health study is a nationwide, multicentre, observational cohort study involving data on individuals aged 18–95 years recruited on a regional community basis from all the territory of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 122.3 ± 66.9 months. Results: A total of 23 467 individuals were included in the analysis. Cut-off values of SUA able to discriminate MI status were identified by mean of receiver operating characteristic curves in the whole database (>5.70 mg/dl), in women (>5.26 mg/dl) and in men (>5.49 mg/dl). Multivariate Cox regression analyses adjusted for confounders (age, arterial hypertension, diabetes, chronic kidney disease, smoking habit, ethanol intake, BMI, haematocrit, LDL cholesterol and use of diuretics) identified an independent association between SUA and fatal MI in the whole database (hazard ratio 1.381, 95% confidence intervals, 1.096–1.758, P = 0.006) and in women (hazard ratio 1.514, confidence intervals 1.105–2.075, P

Introduction Red yeast rice (RYR) is an effective cholesterol-lowering nutraceutical reversibly inhibiting 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase. As liver damage is a possible (albeit rare) side effect of HMG-CoA inhibitors, it make sense to focus on the tolerability of the liver to RYR extracts. The aim of this paper is to offer an expert opinion on the risk of liver damage by the use of RYR extract. Methods A review of the available literature has been carried out and critically reviewed by the authors. Results According to a large meta-analysis of 53 randomized clinical trials comprising 112 treatment arms, which included 8535 subjects with 4437 in the RYR arm and 4303 in the control arm of the study, RYR administration was not associated with increased risk of Drug Induced Liver Injury (DILI) during RYR treatment. Single cases of DILI have been associated with the use of RYR supplements. Even if the causal relationship is hardly demonstrable, it is possible that products containing impurities or toxic elements such as citrinin or unstandardized dosages of bioactive compounds like monacolins, could be implicated in liver toxicity. Conclusion DILI associated with RYR intake are exceptional and hardly associated to RYR per se rather than to low-quality products. Nutrivigilance and stricter manufacturing regulations should be implemented and are recommended in order to protect consumers from low quality and potentially dangerous dietary supplements.

BACKGROUND AND AIMS: Target and intensity of low-density lipoprotein cholesterol (LDL-C) lowering therapy should be tailored according to the individual global cardiovascular (CV) risk. We aimed at retrospectively evaluating real-life LDL-C goal attainment and predictive factors for predefined LDL-C therapeutic goals both in primary and secondary prevention. METHODS: We collected data from a large cohort of outpatients aged 40-65 years, followed by general practitioners, cardiologists and diabetologists in Italy. All data were centrally analysed for global CV risk assessment and rates of control of major CV risk factors, including LDL-C. Study population was stratified according to the presence or absence of previous CV events, including coronary artery disease (CAD), peripheral artery disease (PAD) or stroke/TIA. CV risk profile characterization was based on the European SCORE. Predefined therapeutic goals were set according to the European guidelines on dyslipidaemia: LDL-C levels