Permeability of P. gingivalis or its metabolic products through collagen and dPTFE membranes and their effects on the viability of osteoblast-like cells: an in vitro study.

Membrane exposure is a widely reported and relatively common complication in Guided Bone Regeneration (GBR) procedures. The introduction of micro-porous dPTFE barriers, which are impervious to bacterial cells, could reduce the technique sensitivity to membrane exposure, even if there are no studies investigating the potential passage of bacterial metabolites through the barrier. Aim of this study was the in vitro evaluation of the permeability of three different GBR membranes (dPTFE, native and cross-linked collagen membranes) to Porphyromonas gingivalis; in those cases, where bacterial penetration could not be observed, another purpose was the analysis of the viability and differentiation capability of an osteosarcoma (U2OS) cell line in presence of bacteria eluate obtained through membrane percolation. A system leading to the percolation of P. gingivalis broth culture through the experimental membranes was arranged to assess the permeability to bacteria after 24 and 72 h of incubation. The obtained solution was then added to U2OS cell cultures which underwent, after 10 days of incubation, MTT and red alizarin essays. The dPTFE membrane showed resistance to bacterial penetration, while both types of collagen membranes were crossed by P. gingivalis after 24 h. The bacteria eluate filtered through dPTFE membrane didn't show any toxicity on U2OS cells. Results of this study demonstrate that dPTFE membranes can contrast the penetration of both P. gingivalis and its metabolites toxic for osteoblast-like cells. The toxicity analysis was not possible for the collagen membranes, since permeability to bacterial cells was observed within the first period of incubation.

FOXC2 Disease Mutations Identified in Lymphedema Distichiasis Patients Impair Transcriptional Activity and Cell Proliferation.

FOXC2 is a member of the human forkhead-box gene family and encodes a regulatory transcription factor. Mutations in FOXC2 have been associated with lymphedema distichiasis (LD), an autosomal dominant disorder that primarily affects the limbs. Most patients also show extra eyelashes, a condition known as distichiasis. We previously reported genetic and clinical findings in six unrelated families with LD. Half the patients showed missense mutations, two carried frameshift mutations and a stop mutation was identified in a last patient. Here we analyzed the subcellular localization and transactivation activity of the mutant proteins, showing that all but one (p.Y109*) localized to the nucleus. A significant reduction of transactivation activity was observed in four mutants (p.L80F, p.H199Pfs*264, p.I213Tfs*18, p.Y109*) compared with wild type FOXC2 protein, while only a partial loss of function was associated with p.V228M. The mutant p.I213V showed a very slight increase of transactivation activity. Finally, immunofluorescence analysis revealed that some mutants were sequestered into nuclear aggregates and caused a reduction of cell viability. This study offers new insights into the effect of FOXC2 mutations on protein function and shows the involvement of aberrant aggregation of FOXC2 proteins in cell death.

Inhibition of Anthracycline Alcohol Metabolite Formation in Human Heart Cytosol: A Potential Role for Several Promising Drugs.

The clinical efficacy of anthracyclines (e.g., doxorubicin and daunorubicin) in cancer therapy is limited by their severe cardiotoxicity, the etiology of which is still not fully understood. The development of anthracycline-induced cardiomyopathy has been found to correlate with myocardial formation and accumulation of anthracycline secondary alcohol metabolites (e.g., doxorubicinol and daunorubicinol) that are produced by distinct cytosolic NADPH-dependent reductases. The aim of the current study is to identify chemical compounds capable of inhibiting myocardial reductases implied in anthracycline reductive metabolism in an attempt to decrease the production of cardiotoxic C-13 alcohol metabolites. Among the variety of tested compounds (metal chelators, radical scavengers, antioxidants, ß-blockers, nitrone spin traps, and lipid-lowering drugs), ebselen, cyclopentenone prostaglandins, nitric oxide donors, and short-chain coenzyme Q analogs resulted in being effective inhibitors of both doxorubicinol and daunorubicinol formation. In particular, ebselen (as well as ebselen diselenide, its storage form in the cells) was the most potent inhibitor of cardiotoxic anthracycline alcohol metabolites with 50% inhibition of doxorubicinol formation at 0.2 mol Eq of ebselen with respect to doxorubicin concentration. The high efficacy, together with its favorable pharmacological profile (low toxicity, lack of adverse effects, and metabolic stability) portends ebselen as a promising cardioprotective agent against anthracycline-induced cardiotoxicity.

Cancer Biomarkers Discovery and Validation: State of the Art, Problems and Future Perspectives.

Cancer is one of the major public health problems worldwide representing the leading cause of morbidity and mortality in industrialized countries. To reduce cancer morbidity and mortality as well as to facilitate the evolution from the traditional "one size fits all" strategy to a new "personalized" cancer therapy (i.e., the right drug to the right patient at the right time, using the right dose and schedule), there is an urgent need of reliable, robust, accurate and validated cancer biomarker tests.Unfortunately, despite the impressive advances in tumor biology research as well as in high-powerful "omics" technologies, the translation of candidate cancer biomarkers from bench to bedside is lengthy and challenging and only a few tumor marker tests have been adopted successfully into routine clinical care of oncologic patients.This chapter provides an updated background on biomarkers research in oncology, including biomarkers clinical uses, and discusses the problems of discovery pipeline, biomarkers failures and future perspectives.

The time course of irisin release after an acute exercise: relevant implications for health and future experimental designs.

This study aimed to analyze the acute impact of exercise on serum irisin levels in 22 young (YA, 24.6 ± 3.5 yrs) and in 12 middle-aged male adults (MA, 54.6 ± 5.7 yrs) 15 min and 24 h after an incremental cycling exercise test to exhaustion. ELISA assay was used for serum irisin detection. Circulating irisin increased significantly from baseline (9.0 ± 2.0 ng/ml) to 15 min post-exercise (10.2 ± 2.0 ng/ml, P < 0.001), but the greatest increment was detected after 24 h (13.5 ± 2.5 ng/ml, P < 0.001) reaching more than 50% of the basal release. Levels were significantly higher in YA (9.7 ± 1.7 to 11.1 ± 1.8 to 14.5 ± 2.2 ng/ml) than MA (7.6 ± 1.6 to 8.7 ± 1.5 to 11.8± 2.2 ng/ml) for all measured time-points (P < 0.05). Nevertheless, MA showed a comparable increase in serum irisin levels when compared to YA. These findings highlight the importance of acute physical exercise as a countermeasure against age-related deterioration of skeletal muscle mass and function in both YA and MA.

Myocardial performance index and biochemical markers for early detection of doxorubicin-induced cardiotoxicity in children with acute lymphoblastic leukaemia.

BACKGROUND: Despite significant improvements in the prognosis of childhood acute lymphoblastic leukaemia (ALL), the risk of anthracycline-induced cardiovascular disease remains a major concern. This study was designed to investigate the role of the myocardial performance index (MPI) and serum concentrations of biomarkers (cTnT and NT-pro-BNP) in the early detection of subclinical anthracycline-induced functional alterations in children with ALL. METHODS: All children consecutively admitted to our Pediatric Oncologic Department from January 2009 to October 2010 with a diagnosis of ALL were enrolled in this study. cTnT and NT-pro-BNP were evaluated in all patients at diagnosis, before doxorubicin therapy and 2 and 24 h following each anthracycline administration. ECG and echocardiography were performed at diagnosis and 24 h after each anthracycline course. RESULTS: Nineteen children with standard-risk ALL were evaluated. The mean age was 6 years. The cumulative doxorubicin dosage was 240 mg/m(2) according to the AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica) ALL 2000 protocol. None of the 19 patients developed congestive heart failure. With increasing cumulative dosages of anthracyclines a significant increase was observed in MPI. This increase was statistically significant starting from the cumulative dosage of 120 mg/m(2) compared to baseline, while the median NT-pro-BNP level did not change significantly during treatment and cTnT levels never exceeded the cut-off value for cardiac injury. CONCLUSION: MPI value is a sensitive and accurate parameter, allowing subclinical cardiac dysfunction to be detected in children receiving anthracyclines. Lifelong cardiac surveillance of these patients is warranted in order to determine the clinical implications of increased MPI on long-term cardiac status.

Oral Mucosa Models to Evaluate Drug Permeability.

Due to its numerous advantages, such as excellent drug accessibility, rapid absorption, and bypass of first-pass metabolism, the route of drug administration that involves crossing the oral mucosa is highly favored. As a result, there is significant interest in investigating the permeability of drugs through this region. The purpose of this review is to describe the various ex vivo and in vitro models used to study the permeability of conveyed and non-conveyed drugs through the oral mucosa, with a focus on the most effective models. Currently, there is a growing need for standardized models of this mucosa that can be used for developing new drug delivery systems. Oral Mucosa Equivalents (OMEs) may provide a promising future perspective as they are capable of overcoming limitations present in many existing models.

Salivary and serum irisin in healthy adults before and after exercise.

Irisin is an exercise-induced cytokine mainly secreted by myocytes. Circulating level of irisin can increase in response to acute exercise, promoting pleiotropic effects on health. Generally, irisin is evaluated in blood, however, its collection is invasive. Saliva sample would not have any risk associated with blood collection and would represent a less invasive method for irisin detection. Until now, there are only a few studies that have analyzed irisin levels in saliva. In the present research, five healthy male adults performed an incremental exercise until exhaustion on cycle ergometer. Serum and saliva samples were collected before exercise and 15min, 24h and 48h after reaching the exhaustion. Irisin was detected by ELISA assay. Serum and salivary irisin levels increased from baseline to 24h post exercise and reverted to basal levels after 48h of rest. A significant rise of both serum and salivary irisin level at 24h (p≤0.05) compared to baseline levels was found. Furthermore, a significant correlation between irisin percentage change in serum and saliva from baseline to 24h post exercise was detected (r=0.92, p<0.05). Despite the relatively limited sample, this research suggests that collecting saliva samples might represent a valid and less invasive method to detect irisin level changes induced by exercise.

Anthracyclines and mitochondria.

Anthracyclines remain the cornerstone in the treatment of many malignancies including lymphomas, leukaemias, and sarcomas. Unfortunately, the clinical use of these potent chemotherapeutics is severely limited by the development of a progressive dose-dependent cardiomyopathy that irreversibly evolves toward congestive heart failure. The molecular mechanisms responsible for anthracycline anticancer activity as well as those underlying anthracycline-induced cardiotoxicity are incompletely understood and remain a matter of remarkable controversy. Anthracyclines have long been considered to induce cardiotoxicity by mechanisms different from those mediating their anticancer activity. In particular, anthracycline antitumor efficacy is associated with nuclear DNA intercalation, topoisomerase II inhibition and drug-DNA adducts formation, whereas the cardiotoxicity is prevalently ascribed to oxidative stress and mitochondrial dysfunction. At present, however, the view that distinct mechanisms are implied in anticancer and cardiotoxic responses to anthracycline therapy does not seem fully convincing since beneficial (anticancer) and detrimental (cardiotoxic) effects are to some extent overlapping, share the subcellular organelle targets, the molecular effectors and the pathophysiological processes (i.e. DNA strand breaks, oxidative stress, signalling pathways, mitochondrial dysfunctions, apoptosis etc.).Here, we review the potential role of mitochondria in the molecular mechanisms underlying anthracyclines anticancer activity as well as in the pathogenesis of anthracycline-induced cardiotoxicity.

The Relationship between ACE, ACTN3 and MCT1 Genetic Polymorphisms and Athletic Performance in Elite Rugby Union Players: A Preliminary Study.

Athletic performance is influenced by many factors such as the environment, diet, training and endurance or speed in physical effort and by genetic predisposition. Just a few studies have analyzed the impact of genotypes on physical performance in rugby. The aim of this study was to verify the modulation of genetic influence on rugby-specific physical performance. Twenty-seven elite rugby union players were involved in the study during the in-season phase. Molecular genotyping was performed for: angiotensin-converting enzyme (ACE rs4646994), alfa-actinin-3 (ACTN3 rs1815739) and monocarboxylate transporter 1 (MCT1 rs1049434) and their variants. Lean mass index (from skinfolds), lower-limb explosive power (countermovement jump), agility (505), speed (20 m), maximal aerobic power (Yo-yo intermittent recovery test level 1) and repeated sprint ability (12 × 20 m) were evaluated. In our rugby union players ACE and ACTN3 variants did not show any influence on athletic performance. MCT1 analysis showed that TT-variant players had the highest peak vertical power (p = 0.037) while the ones with the AA genotype were the fastest in both agility and sprint tests (p = 0.006 and p = 0.012, respectively). Considering the T-dominant model, the AA genotype remains the fastest in both tests (agility: p = 0.013, speed: p = 0.017). Only the MCT1 rs1049434 A allele seems to be advantageous for elite rugby union players, particularly when power and speed are required.

Cytotoxic Evaluation of the New Composite Resin through an Artificial Pulp Chamber.

The aim of this study was to analyse the cytocompatibility of Surefil One (SuO) with respect to the release of monomers from the material. The following reference materials were chosen: SDR Flow Plus (SDR, Dentsply Sirona, Konstanz, Germany), One Q Bond (Q, Dentalica, Milan, Italy), and Ketac (K, 3M-ESPE, USA). Fifteen dentin discs (2 mm thickness and diameter) were obtained from 15 third molars and were used in this study. After dentin disc permeability measurement, murine fibroblasts were grown, and the pulp surface of the dentinal disc was placed in direct contact with the cells immersed in DMEM. The experimental materials were positioned on the occlusal side of each dentinal disc until a uniform thickness of 2 mm was obtained. Then, the discs were inserted into an artificial pulp chamber for 24 hours to assess the cytocompatibility. Afterwards, the moles of monomers leached from the specimens in DMEM were determined using HPLC. Statistical analysis was performed using ANOVA (p < 0.05). Under the experimental conditions, the toxic effect induced by all tested materials was slight or absent. Diurethane dimethacrylate and acrylic acid were not found in the culture media. It is concluded that all materials have good cytocompatibility consistent with the nondeterminability of the monomers released after polymerization.

Circulating irisin levels in functional hypothalamic amenorrhea: a new bone damage index? A pilot study.

PURPOSE: Patients with functional hypothalamic amenorrhea (FHA) could commonly have bone damage, often preceded by metabolic alterations due to a relative energy deficit state. To date, there are no markers capable of predicting osteopenia before it is manifested on DXA. Irisin is a myokine that promotes the differentiation of osteoblastic cells and appears to be inversely correlated with the incidence of bone fragility and fractures in postmenopausal women. The aim of this study was to measure irisin levels in FHA patients and to correlate it with bone density parameters. METHODS: Thirty-two patients with FHA and 19 matched controls underwent the same clinical and laboratory evaluation. RESULTS: Irisin and body mass index (BMI) were significantly lower in the case group than in healthy controls (2.03 ± 0.12 vs. 2.42 ± 0.09 p < 0.05 and 19.43 ± 2.26 vs. 22.72 ± 0.67 p < 0.05, respectively). Additionally, total body mass density (BMD g/cm2) was significantly lower in the case group than in the healthy controls (1.09 ± 0.08 vs. 1.14 ± 0.05, p < 0.05), without signs of osteopenia. CONCLUSIONS: The FHA group showed lower irisin levels associated with significantly reduced BMD parameters that did not reach the severity of osteopenia. Therefore, we could speculate that irisin could predict DXA results in assessing modifications of body composition parameters. Future research is warranted to study these parameters in a larger population to confirm our results, so that irisin could be used as a predictor and screening method for bone deprivation. Furthermore, irisin is strictly related to energy metabolism and could be an indirect marker of nutritional status in FHA patients, identifying earlier states of energy deficit.

Determination of asymmetric dimethyl arginine in human serum by liquid chromatography-tandem mass spectrometry: clinical application in hypertensive subjects.

BACKGROUND: Asymmetric dimethylarginine (ADMA), an endogenous competitive inhibitor of nitric oxide synthase plays an important role in endothelial dysfunction processes. Recent studies have linked high ADMA levels with several pathological conditions. The interest as a marker of endothelial dysfunction has increased in the last few years. In this paper, a method for serum ADMA quantification by liquid chromatography tandem mass spectrometry has been described. To test the utility in a pathological condition ADMA levels in hypertensive subjects have been measured. METHODS: HPLC separation was performed by hydrophilic interaction chromatography using acetonitrile/water containing 0.1% formic acid and 20 mmol/L ammonium formate. Selected reaction monitoring was performed following the transitions m/z 203.1→46.4 for ADMA and 210.1→46.3 for the internal standard [2H7]ADMA. RESULTS: The method was linear up to 10 µmol/L, limit of detection and limit of quantification were 0.005 µmol/L and 0.01 µmol/L, respectively. Recovery was higher than 96%. Intra- and inter-assay imprecision were lower than 6%. The accuracy, expressed as bias %, was <2.5. ADMA in "healthy" subjects ranged from 0.343 to 0.608 µmol/L and resulted significantly lower than that measured in hypertensive subjects (p<0.001). CONCLUSIONS: The method developed is selective and sensitive, thus suitable not only for research purposes, but also for routinely work.

Controlled Release of 18-ß-Glycyrrhetinic Acid from Core-Shell Nanoparticles: Effects on Cytotoxicity and Intracellular Concentration in HepG2 Cell Line.

18ß-glycyrrhetinic acid (GA) is a pentacyclic triterpene with promising hepatoprotective and anti-Hepatocellular carcinoma effects. GA low water solubility however reduces its biodistribution and bioavailability, limiting its applications in biomedicine. In this work we used core-shell NPs made of PolyD-L-lactide-co-glycolide (PLGA) coated with chitosan (CS), prepared through an osmosis-based methodology, to efficiently entrap GA. NPs morphology was investigated with SEM and TEM and their GA payload was evaluated with a spectrophotometric method. GA-loaded NPs were administered to HepG2 cells and their efficiency in reducing cell viability was compared with that induced by the free drug in in vitro tests. Cell viability was evaluated by the MTT assay, as well as with Electric Cells-Substrate Impedance Sensing (ECIS), that provided a real-time continuous monitoring. It was possible to correlate the toxic effect of the different forms of GA with the bioavailability of the drug, evidencing the importance of real-time tests for studying the effects of bioactive substances on cell cultures.

Can plasma antioxidants prevent DNA damage in oxidative stress condition induced by growth hormone deficiency? A pilot study.

Adult growth hormone deficiency (GHD), a condition characterized by increased oxidative stress, is related to augmented cardiovascular, metabolic and oncological risk. A case-control observational study has been performed to evaluate DNA oxidative damage analysing the production of thymidine-glycol in lymphocytes and its correlation with plasma antioxidant levels, evaluated as Total Antioxidant Capacity (TAC). GHD was diagnosed using GHRH 50µg iv+arginine 0,5 g/Kg test, with peak GH response <9 µg/L when BMI was <30 kg/m2 or <4 µg/L when BMI was >30 kg/m2. Three groups were identified: total GHD (n = 16), partial GHD (n = 11), and controls (n = 12). Thymidine-glycol, TAC and IGF-1 have been determined respectively in lymphocytes, plasma and serum samples. When considering thymidine-glycol, we found a significant difference between total vs partial GHD and controls. Unexpectedly thymidine-glycol was lower in total GHD, also accompanied with a significant increase in plasmatic TAC. Our results showed that in adult GHD condition, the production of antioxidant species, in response to increased oxidative stress, could exert a protective effect on thymidine-glycol formation, and consequently on DNA intracellular damages. This pilot study could be inserted in the complex scenario of oxidative damage of GHD, a subtle, yet poorly defined condition, worthy of further insights.

Structural determinants driving the binding process between PDZ domain of wild type human PALS1 protein and SLiM sequences of SARS-CoV E proteins.

Short Linear Motifs (SLiMs) are functional protein microdomains that typically mediate interactions between a short linear region in one protein and a globular domain in another. Surface Plasmon Resonance assays have been performed to determine the binding affinity between PDZ domain of wild type human PALS1 protein and tetradecapeptides representing the SLiMs sequences of SARS-CoV-1 and SARS-CoV-2 E proteins (E-SLiMs). SARS-CoV-2 E-SLiM binds to the human target protein with a higher affinity compared to SARS-CoV-1, showing a difference significantly greater than previously reported using the F318W mutant of PALS1 protein and shorter target peptides. Moreover, molecular dynamics simulations have provided clear evidence of the structural determinants driving this binding process. Specifically, the Arginine 69 residue in the SARS-CoV-2 E-SLiM is the key residue able to both enhance the specific polar interaction with negatively charged pockets of the PALS1 PDZ domain and reduce significantly the mobility of the viral peptide. These experimental and computational data are reinforced by the comparison of the interaction between the PALS1 PDZ domain with the natural ligand CRB1, as well as the corresponding E-SLiMs of other coronavirus members such as MERS and OCF43. Our results provide a model at the molecular level of the strategies used to mimic the endogenous SLiM peptide in the binding of the tight junctions of the host cell, explaining one of the possible reasons of the severity of the infection and pulmonary inflammation by SARS-CoV-2.

Is There Room for SERMs or SARMs as Alternative Therapies for Adult Male Hypogonadism?

Hypogonadotropic hypogonadism (HH) can be sustained by organic or functional alterations of the hypothalamic-pituitary-testicular axis. Functional HH is related to systemic alterations, such as obesity or chronic inflammatory diseases, but could contribute to a negative course of the illness. For such situation, according to results obtained in infertile women, the administration of selective estrogen receptor modulators (SERMs) has been proposed in males too, with positive results on both metabolic and sexual function. This class of medications increases gonadotropin levels via antagonism to the estrogenic receptor; similar biological effects are also exerted by aromatase inhibitors (AIs), despite different mechanism of action. After a brief review of trials regarding SERMs and AIs use in male HH, we describe the structure and function of the androgen receptor (AR) as a basis for clinical research about compounds able to bind to AR, in order to obtain specific effects (SARMs). The tissue selectivity and different metabolic fate in comparison to testosterone can potentiate anabolic versus androgenic effects; therefore, they might be a valid alternative to testosterone replacement therapy avoiding the negative effects of testosterone (i.e., on prostate, liver, and hematopoiesis). Trials are still at an early phase of investigation and, at the moment, the application seems to be more useful for chronic disease with catabolic status while the validation as replacement for hypogonadism requires further studies.

The Role of Selenium in Oxidative Stress and in Nonthyroidal Illness Syndrome (NTIS): An Overview.

Selenium is a trace element, nutritionally classified as an essential micronutrient, involved in maintaining the correct function of several enzymes incorporating the selenocysteine residue, namely the selenoproteins. The human selenoproteome including 25 proteins is extensively described here. The most relevant selenoproteins, including glutathione peroxidases, thioredoxin reductases and iodothyronine deiodinases are required for the proper cellular redox homeostasis as well as for the correct thyroid function, thus preventing oxidative stress and related diseases. This review summarizes the main advances on oxidative stress with a focus on selenium metabolism and transport. Moreover, thyroid-related disorders are discussed, considering that the thyroid gland contains the highest selenium amount per gram of tissue, also for future possible therapeutic implication.

Low Molecular Weight Dextran Sulfate (ILB®) Administration Restores Brain Energy Metabolism Following Severe Traumatic Brain Injury in the Rat.

Traumatic brain injury (TBI) is the leading cause of death and disability in people less than 40 years of age in Western countries. Currently, there are no satisfying pharmacological treatments for TBI patients. In this study, we subjected rats to severe TBI (sTBI), testing the effects of a single subcutaneous administration, 30 min post-impact, of a new low molecular weight dextran sulfate, named ILB®, at three different dose levels (1, 5, and 15 mg/kg body weight). A group of control sham-operated animals and one of untreated sTBI rats were used for comparison (each group n = 12). On day 2 or 7 post-sTBI animals were sacrificed and the simultaneous HPLC analysis of energy metabolites, N-acetylaspartate (NAA), oxidized and reduced nicotinic coenzymes, water-soluble antioxidants, and biomarkers of oxidative/nitrosative stress was carried out on deproteinized cerebral homogenates. Compared to untreated sTBI rats, ILB® improved energy metabolism by increasing ATP, ATP/ adenosine diphosphate ratio (ATP/ADP ratio), and triphosphate nucleosides, dose-dependently increased NAA concentrations, protected nicotinic coenzyme levels and their oxidized over reduced ratios, prevented depletion of ascorbate and reduced glutathione (GSH), and decreased oxidative (malondialdehyde formation) and nitrosative stress (nitrite + nitrate production). Although needing further experiments, these data provide the first evidence that a single post-injury injection of a new low molecular weight dextran sulfate (ILB®) has beneficial effects on sTBI metabolic damages. Due to the absence of adverse effects in humans, ILB® represents a promising therapeutic agent for the treatment of sTBI patients.

Anabolic Hormones Deficiencies in Heart Failure With Preserved Ejection Fraction: Prevalence and Impact on Antioxidants Levels and Myocardial Dysfunction.

Purpose: In heart failure with reduced ejection fraction, catabolic mechanisms have a strong negative impact on mortality and morbidity. The relationship between anabolic hormonal deficiency and heart failure with preserved ejection fraction (HFpEF) has still been poorly investigated. On the other hand, oxidative stress is recognized as a player in the pathogenesis of HFpEF. Therefore, we performed a cohort study in HFpEF aimed to (1) define the multi-hormonal deficiency prevalence in HFpEF patients; (2) investigate the relationships between hormonal deficiencies and echocardiographic indexes; (3) explore the modulatory activity of anabolic hormones on antioxidant systems. Methods: 84 patients with diagnosis of HFpEF were enrolled in the study. Plasma levels of N-terminal pro-brain natriuretic peptide, fasting glucose, insulin, lipid pattern, insulin-like growth factor-1, dehydroepiandrosterone-sulfate (DHEA-S), total testosterone (T, only in male subjects) were evaluated. Hormonal deficiencies were defined according to T.O.S.C.A. multi-centric study, as previously published. An echocardiographic evaluation was performed. Plasma total antioxidant capacity (TAC) was measured using the system metmyoglobin -H2O2 and the chromogen ABTS, whose radical form is spectroscopically revealed; latency time (LAG) in the appearance of ABTS• is proportional to antioxidants in sample. Results: Multiple deficiencies were discovered. DHEA-S deficiency in 87% of patients, IGF-1 in 67% of patients, T in 42%. Patients with DHEA-S deficiency showed lower levels of TAC expressed by LAG (mean ± SEM 91.25 ± 9.34 vs. 75.22 ± 4.38 s; p < 0.05). No differences between TAC in patients with or without IGF-1 deficiency were found. A trend toward high level of TAC in patients without hormonal deficiencies compared with patients with one or multiple deficiencies was found. Regarding echocardiographic parameters, Left Atrial and Left Atrial Volume Index were significantly higher in patients with low IGF-1 values (mean ± SD 90.84 ± 3.86 vs. 72.83 ± 3.78 mL; 51.03 ± 2.33 vs. 40.56 ± 2.46 mL/m2, respectively; p < 0.05). Conclusions: Our study showed high prevalence of anabolic deficiencies in HFpEF. DHEA-S seems to influence antioxidant levels; IGF-1 deficiency was associated with alteration in parameters of myocardial structure and dysfunction. These data suggest a role of anabolic hormones in the complex pathophysiological mechanisms of HFpEF and could represent the basis for longitudinal studies and investigations on possible benefits of replacement therapy.