Frog Skin-Derived Peptides Against Corynebacterium jeikeium: Correlation between Antibacterial and Cytotoxic Activities.

Corynebacterium jeikeium is a commensal bacterium that colonizes human skin, and it is part of the normal bacterial flora. In non-risk subjects, it can be the cause of bad body smell due to the generation of volatile odorous metabolites, especially in the wet parts of the body that this bacterium often colonizes (i.e., groin and axillary regions). Importantly, in the last few decades, there have been increasing cases of serious infections provoked by this bacterium, especially in immunocompromised or hospitalized patients who have undergone installation of prostheses or catheters. The ease in developing resistance to commonly-used antibiotics (i.e., glycopeptides) has made the search for new antimicrobial compounds of clinical importance. Here, for the first time, we characterize the antimicrobial activity of some selected frog skin-derived antimicrobial peptides (AMPs) against C. jeikeium by determining their minimum inhibitory and bactericidal concentrations (MIC and MBC) by a microdilution method. The results highlight esculentin-1b(1-18) [Esc(1-18)] and esculentin-1a(1-21) [Esc(1-21)] as the most active AMPs with MIC and MBC of 4-8 and 0.125-0.25 µM, respectively, along with a non-toxic profile after a short- and long-term (40 min and 24 h) treatment of mammalian cells. Overall, these findings indicate the high potentiality of Esc(1-18) and Esc(1-21) as (i) alternative antimicrobials against C. jeikeium infections and/or as (ii) additives in cosmetic products (creams, deodorants) to reduce the production of bad body odor.

Antimicrobial Peptides and their Multiple Effects at Sub-Inhibitory Concentrations.

The frequent occurrence of multidrug-resistant strains to conventional antimicrobials has led to a clear decline in antibiotic therapies. Therefore, new molecules with different mechanisms of action are extremely necessary. Due to their unique properties, antimicrobial peptides (AMPs) represent a valid alternative to conventional antibiotics and many of them have been characterized for their activity and cytotoxicity. However, the effects that these peptides cause at concentrations below the minimum growth inhibitory concentration (MIC) have yet to be fully analyzed along with the underlying molecular mechanism. In this mini-review, the ability of AMPs to synergize with different antibiotic classes or different natural compounds is examined. Furthermore, data on microbial resistance induction are reported to highlight the importance of antibiotic resistance in the fight against infections. Finally, the effects that sub-MIC levels of AMPs can have on the bacterial pathogenicity are summarized while showing how signaling pathways can be valid therapeutic targets for the treatment of infectious diseases. All these aspects support the high potential of AMPs as lead compounds for the development of new drugs with antibacterial and immunomodulatory activities.

Association between epicardial fat thickness and cognitive function in elderly. A preliminary study.

BACKGROUND: Recent studies suggested that the visceral fat could exert a predictive role in the pathogenesis of dementia. The aims of the present study were to evaluate: i) possible differences between groups with different epicardial adipose tissue (EAT) thickness on the included variables; ii) the possible predictive role of the EAT levels on cognitive functioning. METHODS: 65 community-dwelling subjects were enrolled and divided into two groups: EAT < 7 mm (n = 36); EAT > 7 mm (n = 29). The metabolic profile was assessed through the evaluation of the biochemical parameters whereas the EAT thickness was measured through the transthoracic echocardiography. The Mini Mental State Examination (MMSE) was also administered. RESULTS: The two EAT groups reported several significant differences, included on the MMSE scores. The multiple linear regression analysis showed that the EAT thickness levels and the hypertension had a predictive effect on the MMSE scores. CONCLUSIONS: These preliminary findings support the association between EAT thickness levels and cognitive impairment.

Thyroid hormones, metabolic syndrome and Vitamin D in middle-aged and older euthyroid subjects: a preliminary study.

AIM: To explore the relationship between thyroid hormones, Vitamin D (Vit.D) serum concentrations and metabolic syndrome (MetS) in euthyroid subjects. METHODS: 123 community-dwelling subjects were enrolled. According to thyroid-stimulating hormone (TSH) values the sample was divided into: (1) group 1 (TSH ≤ 2 mU/L); (2) group 2 (TSH > 2 mU/L). RESULTS: Group 2 showed higher percentage of subjects with MetS (p = 0.003) and hypertension (p = 0.031), higher values of waist circumference (WC) (p = 0.007), parathyroid hormone (p = 0.016), glycaemia (p = 0.045), triglycerides (p = 0.034) and free T4 (fT4) (p = 0.013). Correlation analysis showed several weak significant correlations: MetS with TSH (r = 0.202, p = 0.031) and fT3 (r = - 0.206, p = 0.028); THS with body mass index (r = 0.187, p = 0.047) and hypertension (r = 0.199, p = 0.034); Vit.D with WC (r = - 0.185, p = 0.04). CONCLUSIONS: Our results showed a possible association between thyroid hormones and MetS. Visceral fat and insulin resistance may be an interesting link between Vit.D and TSH levels.

Esculentin-1a Derived Antipseudomonal Peptides: Limited Induction of Resistance and Synergy with Aztreonam.

BACKGROUND: The massive use of antibiotics has led to the selection of resistant bacterial strains that are difficult to eradicate. Among these, Pseudomonas aeruginosa most frequently colonizes and infects the airways of cystic fibrosis patients. Cationic Antimicrobial Peptides (AMPs) represent interesting molecules for the development of new antimicrobial agents. Thanks to their mechanism of action that involves the permeabilization of the bacterial cytoplasmic membrane, the induction of resistance is quite limited. OBJECTIVE: The evaluation of the capability of two frog-skin derived AMPs, i.e. Esc(1-21) and its diastereomer Esc(1-21)-1c, to induce resistance in P. aeruginosa and synergize with aztreonam. METHOD: The induction of resistance was evaluated after 15 cycles of exposure to non-inhibitory growth concentrations of antibiotics and peptides. Subsequently, the Minimal Inhibitory Concentration (MIC) was calculated and compared to that obtained before drug exposure. Furthermore, MICs of AMPs and antibiotics were evaluated in Artificial Sputum Medium (ASM). Finally, the ability of the two peptides to synergize with aztreonam was determined by the checkerboard titration method. RESULTS: Pseudomonas aeruginosa acquired resistance to antibiotics, as evidenced by the increased MICs compared to the initial ones (from 8 to 128-fold higher), while no change in MICs was observed after multiple treatments with the Esc-peptides. In addition, both peptides showed significantly lower MICs than aztreonam in ASM. Finally, the diastereomer Esc(1-21)-1c had the ability to synergize with aztreonam in inhibiting growth and in killing Pseudomonas cells. CONCLUSION: Both peptides represent promising candidates for the development of new antipseudomonal compounds, which do not induce resistance.

The development of a new tool for the evaluation of handicap in elderly: the Geriatric Handicap Scale (GHS).

BACKGROUND: To date, the comprehensive geriatric assessment (CGA) does not include an evaluation tool for handicap. AIM: To develop a new instrument for assessing handicap in the elderly: the Geriatric Handicap Scale (GHS). METHODS: 656 community-dwelling elderly were enrolled in this study. We identified the thematic areas investigated by the CGA which showed a significant correlation with the handicap condition (handicap yes/not) to be included in our scale (Phase 1). Afterwards, we evaluated the possible correlations between: (1) the score obtained in each area of GHS and those obtained in CGA tests investigating similar dimensions, (2) GHS total score and the Multidimensional Prognostic Index (MPI) total score (Phase 2). RESULTS: In Phase 1, data analysis showed several significant correlations between the handicap condition and the scores obtained to the CGA tests exploring cognition, mood, functional impairment, comorbidity, social and environmental variables. Thus, we developed a tool considering five variables: (1) cognition and mood; (2) functional impairment; (3) hearing/visual impairment; (4) any additional comorbidity factors; (5) environmental/social risk factors. In Phase 2, data analysis showed significant correlations between the score obtained in each area of GHS and those obtained in the CGA tests investigating similar dimensions. A positive correlation between GHS total score and MPI total score (r = 68; p = 0.001) was also reported. Cut-off score for the GHS was established. Psychometric properties of GHS were also investigated and adequate estimates of internal reliability were demonstrated. CONCLUSIONS: Our tool could prove useful to correctly categorize the disadvantageous condition related to patient's disability.

A new tool for the evaluation of the rehabilitation outcomes in older persons: a machine learning model to predict functional status 1 year ahead.

PURPOSE: To date, the assessment of disability in older people is obtained utilizing a Comprehensive Geriatric Assessment (CGA). However, it is often difficult to understand which areas of CGA are most predictive of the disability. The aim of this study is to evaluate the possibility to early predict-1 year ahead-the disability level of a patient using machine leaning models. METHODS: Community-dwelling older people were enrolled in this study. CGA was made at baseline and at 1 year follow-up. After collecting input/independent variables (i.e., age, gender, schooling followed, body mass index, information on smoking, polypharmacy, functional status, cognitive performance, depression, nutritional status), we performed two distinct Support Vector Machine models (SVMs) able to predict functional status 1 year ahead. To validate the choice of the model, the results achieved with the SVMs were compared with the output produced by simple linear regression models. RESULTS: 218 patients (mean age = 78.01; SD = 7.85; male = 39%) were recruited. The combination of the two SVMs is able to achieve a higher prediction accuracy (exceeding 80% instances correctly classified vs 67% instances correctly classified by the combination of the two linear regression models). Furthermore, SVMs are able to classify both the three categories, self sufficiently, disability risk and disability, while linear regression model separates the population only in two groups (self-sufficiency and disability) without identifying the intermediate category (disability risk) which turns out to be the most critical one. CONCLUSIONS: The development of such a model can contribute to the early detection of patients at risk of self-sufficiency loss.

Association between serum vitamin D and metabolic syndrome in middle-aged and older adults and role of supplementation therapy with vitamin D.

OBJECTIVES: To evaluate i) the correlation between vitamin D (vit. D) serum concentrations and metabolic syndrome (MetS); ii) the efficacy of 6 months supplementation therapy with vit. D. METHOD: 200 patients were enrolled. Blood analyses and anthropometric measurements were carried out. Patients with hypovitaminosis D received an oral supplement therapy. RESULTS: 81% of the sample shows vit. D levels < 30 ng/mL. Rate of MetS was significantly higher in vit. D deficiency group than in vit D insufficiency (p = 0.009) and sufficiency (p = 0.002) groups. Vit. D shows a significant negative correlation with both waist circumference (WC) (ρ - 0.202 p = 0.004) and glycaemia values (FBG) (ρ -0.185 p = 0.009). After the supplementation therapy in a group of 60 subjects a significant increase in vit. D levels (p = 0.001) and a significant reduction in WC values (p = 0.001) were observed. CONCLUSIONS: MetS, WC and FBG appeared to be associated vit. D status and it is well-known that central obesity, with the inflammatory alterations thereto correlated that determine insulin resistance, can be considered the "primum movens" for the development of MetS.

Efficacy and safety of spinning exercise in middle-aged and older adults with metabolic syndrome: randomized control trial.

BACKGROUND: Few studies have been conducted to investigate the effects of spinning exercise on cardio-vascular weal. AIM: To assess whether a 6 months spinning training, combined with proper diet, is more effective than standard training programs and diet alone in improving metabolic abnormalities in middle-aged and older adults. DESIGN: Randomized clinical trial. SETTING: Rehabilitation Unit of our Department. POPULATION: Patients with Metabolic Syndrome (MetS) according to the National Cholesterol Education Program Adult Treatment Panel III diagnostic criteria. METHODS: Patients were randomly assigned to receive treatment with diet (group A, n = 10), with diet and general gymnastics program (group B, n = 10), with diet and spinning physical training program (group C, n = 10). RESULTS: During the study period we observed a significant reduction in blood pressure (group C: systolic blood pressure p = 0.03; diastolic blood pressure p = 0.004 / group B: systolic blood pressure p = 0.001), in lipid profile (group B: plasma total cholesterol p = 0.001; triglycerides p = 0.001 / group C: plasma total cholesterol p = 0.04); in fasting blood glucose (group B: p = 0.01; group C: p = 0.008); in Homeostatic Model Assessment of Insulin Resistance (group B: p = 0.01; group C: p = 0.001); in waist circumference (group C: p = 0.005; group A: p = 0.02; group B: p = 0.04). No patients reported adverse events during follow-up. CONCLUSION: Our results confirm the effectiveness of spinning training combined with diet in the management of MetS. CLINICAL REHABILITATION IMPACT: The findings provide a preliminary evidence to support that spinning training may represent a useful and safe intervention also in middle-aged and older adults geriatric with multiple CV risk factors.

Relationship between vitamin D and body fat distribution evaluated by DXA in postmenopausal women.

OBJECTIVE: The aim of this study was to explore the relationship between 25-hydroxyvitamin D (25[OH]D) serum concentrations and body fat distribution in a sample of postmenopausal women. METHODS: We enrolled sixty-two postmenopausal women; 25(OH)D serum concentrations, serum intact parathyroid hormone, blood analyses, and anthropometric measurements were carried out. Body fat composition was evaluated by dual-energy X-ray absorptiometry. Insulin resistance was estimated by homeostatic model assessment of insulin resistance (HOMA-IR) calculation. RESULTS: Low levels of vitamin D (<30 ng/mL) were found in 77.4% of the population studied. There was a correlation (P < 0.0001) between 25(OH)D and waist circumference (r = -0.543), android fat to gynoid fat (A/G) ratio (r = -0.554), high-density lipoprotein cholesterol (r = 0.498), and HOMA-IR (r = -0.520). A/G fat ratio (B = -34.90; 95% confidence interval [-55.30, -14.1]; P = 0.019), HOMA-IR (B = -3.17; 95% confidence interval [-5.99, -0.351]; P = 0.028), and high-density lipoprotein cholesterol (B = 0.361; 95% confidence interval [0.033, 0.698]; P = 0.032), were found to be independent predictors of lower 25(OH)D by multilogistic regression analysis. Except for waist circumference, both these results were maintained when correlations were adjusted for age, onset of menopause, serum intact parathyroid hormone, and medications, and when body mass index was added as covariate. CONCLUSIONS: Vitamin D deficiency and insufficiency are common conditions. A/G ratio appeared to be associated with 25(OH)D concentrations and it is well-known that the android disposition of body fat is more closely associated with the onset of metabolic syndrome. Longitudinal studies are needed to better characterize the direction and the causal links of this association.

The Mozart Effect: A quantitative EEG study.

The aim of this study is to investigate the influence of Mozart's music on brain activity through spectral analysis of the EEG in young healthy adults (Adults), in healthy elderly (Elderly) and in elderly with Mild Cognitive Impairment (MCI). EEG recording was performed at basal rest conditions and after listening to Mozart's K448 or "Fur Elise" Beethoven's sonatas. After listening to Mozart, an increase of alpha band and median frequency index of background alpha rhythm activity (a pattern of brain wave activity linked to memory, cognition and open mind to problem solving) was observed both in Adults and in Elderly. No changes were observed in MCI. After listening to Beethoven, no changes in EEG activity were detected. This results may be representative of the fact that said Mozart's music is able to "activate" neuronal cortical circuits related to attentive and cognitive functions.

Impact of combined therapy with alpha-lipoic and ursodeoxycolic acid on nonalcoholic fatty liver disease: double-blind, randomized clinical trial of efficacy and safety.

BACKGROUND AND PURPOSE: Nonalcoholic fatty liver disease (NAFLD) is one of the causes of a fatty liver, occurring when fat is deposited (steatosis) in the liver not due to excessive alcohol use. It is related to insulin resistance and the metabolic syndrome. The purpose of the present study was to evaluate the impact of combination therapy with alpha-lipoic acid (ALA) and ursodeoxycholic acid (UDCA) on NAFLD. METHODS: Alpha-lipoic acid 400 mg/day plus UDCA 300 mg/day (ALAUDCA) was investigated in patients over a period of 12 months using a randomized, placebo (PLA)-controlled study with four parallel groups. Serum concentration of gamma-glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin and platelets (PLT) were measured at the beginning and at the end of the treatment. Moreover, the AST/ALT ratio and the NAFLD fibrosis score were examined. RESULTS: A total of 120 patients were randomly assigned to the four groups. ALA and UDCA were safe and well tolerated in the oral daily administration only. AST, ALT, GGT (p < 0.001) showed a significant difference between ALAUDCA and other three groups. Besides, NAFLD fibrosis score underlined a significant reduction (p < 0.04) in the ALAUDCA group, while AST/ALT ratio presented a moderate decline (p > 0.05). CONCLUSION: ALAUDCA therapy reduced AST, ALT, GGT values and improved NAFLD fibrosis score and AST/ALT ratio, especially in patients who were on a hypocaloric diet. These findings will be useful in patient selection in future clinical trials with ALAUDCA in long-term studies.

[Predictors of liver fibrosis in patients with non-alcoholic fatty liver disease. The role of metabolic syndrome, insulin-resistance and inflammation]. / Predittori di fibrosi epatica in pazienti con steatosi epatica non-alcolica. Il ruolo della sindrome metabolica, dell'insulino-resistenza e dell'infiammazione.

INTRODUCTION: NAFLD (non-alcoholic fatty liver disease) reaches an high prevalence in the general population, and it is closely related to metabolic syndrome (MetS). The entity of metabolic abnormalities and the chronic inflammation seem to play a main role in the development of liver fibrosis. The aim of our study is to determine whether subjects with NAFLD and MetS have higher liver fibrosis degree when compared with NAFLD subjects without MetS, and to investigate the relations between fibrosis, MetS and its single components and inflammation. MATERIALS AND METHODS: We considered 24 patients with NAFLD. Those who had viral- and alcohol- related liver disease were excluded. MetS was diagnosed according to NCEP ATP III criteria; inflammatory status was determined through C-reactive protein (PCR) assay. The peripheral insulin-resistance was assessed by calculating HOMA ir. Liver fibrosis was measured by transient elastography (Fibroscan®). RESULTS: Subjects with MetS had higher HOMA ir, PCR and Fibroscan® score (log value: 0.92±0.24 KPa vs 0.73±0.2 KPa; p=0.047). The linear correlation analysis showed that Fibroscan® score was related to MetS, number of MetS components, waist circumference, HOMA ir and PCR. However the multivariate regression analysis showed that only HOMA ir (B=0.077; 95%CI: -0.002- 0.157; p=0.05) and PCR (B=0.152; 95% CI: 0.006 - 0.299; p=0.006) were independent predictors of higher Fibroscan® score. CONCLUSION: MetS is associated to higher liver fibrosis degree in subjects with NAFLD. The insulin-resistance and inflammation seem to be the main determinants.