Effects of Age, Age-Related Hearing Loss, and Contralateral Cafeteria Noise on the Discrimination of Small Frequency Changes: Psychoacoustic and Electrophysiological Measures

The aim of the study was to examine central auditory processes compromised by age, age-related hearing loss, and the presentation of a distracting cafeteria noise using auditory event-related potentials (ERPs). In addition, the relation of ERPs to behavioral measures of discrimination was investigated. Three groups of subjects participated: young normal hearing, elderly subjects with normal hearing for their age, and elderly hearing-impaired subjects. Psychoacoustic frequency discrimination thresholds for a 1000-Hz pure tone were determined in quiet and in the presence of a contralateral cafeteria noise. To elicit ERPs, small frequency contrasts were presented with and without noise under unattended and attended conditions. In the attended condition, behavioral measures of d′ detectability and reaction times were also obtained. Noise affected all measures of behavioral frequency discrimination significantly. Except N1, all ERP components in the standard and difference waveforms decreased significantly in amplitude and increased in latency to the same degree in all three subject groups, arguing against a specific age-related sensitivity to the effects of contralateral background noise. For N1 amplitude, the effect of noise was different in the three subject groups, with a complex interaction of age, hearing loss, and attention. Behavioral frequency discrimination was not affected by age but deteriorated significantly in the elderly subjects with hearing loss. In the electrophysiological test, age-related changes occurred at various levels. The most prominent finding in the response to the standard stimuli was a sustained negativity (N2) following P2 in the young subjects that was absent in the elderly, possibly indicating a deficit in the inhibition of irrelevant information processing. In the attended difference waveform, significantly larger N2b and smaller P3b amplitudes and longer N2b and P3b latencies were observed in the elderly indicating different processing strategies. The pronounced age-related changes in the later cognitive components suggest that the discrimination of difficult contrasts, although behaviorally maintained, becomes more effortful in the elderly.     

Licoflavone C attenuates the genotoxicity of cancer drugs in human peripheral lymphocytes

Flavonoids exhibit a wide spectrum of biological activities that can lead to beneficial effects for human health. The search for cytotoxic, genotoxic and/or antimutagenic natural compounds is therefore of great relevance, especially in cancer chemotherapy. In view of this, we screened the potential genotoxicity/antigenotoxicty of licoflavone C (LFLC) - a naturally occurring prenyl-flavone extracted from Genista ephedroides - using the micronucleus (MN) assay on stimulated and cytochalasin B-blocked human lymphocytes. LFLC did not increase the spontaneous MN level up to 600 microM final concentration where a strong toxicity was seen to occur. We therefore performed an antigenotoxicity assay against the two mutagenic anticancer drugs, mitomycin C (MMC) and daunorubicin (DAU), using two non-toxic LFLC concentrations (0.1 microM and 1.0 microM). The MN frequencies induced by 0.025 microg/ml or 0.05 microg/ml DAU were significantly lowered by 45.4% or 46.6% and 41.8% or 44.8% at LFLC 0.1 and 1.0 microM, respectively. After treatment with 0.085 microg/ml or 0.17 microg/ml MMC, we detected a reduction in genotoxicity of 35.1% or 37.0% and of 38.0% or 35.8% at LFLC 0.1 and 1.0 microM, respectively. In conclusion, LFLC was proven to be protective toward the chromosome damage induced by DAU or MMC in cultured human peripheral lymphocytes.     

The CHD8 overgrowth syndrome: A detailed evaluation of an emerging overgrowth phenotype in 27 patients

CHD8 has been reported as an autism susceptibility/intellectual disability gene but emerging evidence suggests that it additionally causes an overgrowth phenotype. This study reports 27 unrelated patients with pathogenic or likely pathogenic CHD8 variants (25 null variants, two missense variants) and a male:female ratio of 21:6 (3.5:1, p < .01). All patients presented with intellectual disability, with 85% in the mild or moderate range, and 85% had a height and/or head circumference ≥2 standard deviations above the mean, meeting our clinical criteria for overgrowth. Behavioral problems were reported in the majority of patients (78%), with over half (56%) either formally diagnosed with an autistic spectrum disorder or described as having autistic traits. Additional clinical features included neonatal hypotonia (33%), and less frequently seizures, pes planus, scoliosis, fifth finger clinodactyly, umbilical hernia, and glabellar hemangioma (≤15% each). These results suggest that, in addition to its established link with autism and intellectual disability, CHD8 causes an overgrowth phenotype, and should be considered in the differential diagnosis of patients presenting with increased height and/or head circumference in association with intellectual disability.     

Virgin olive oil minor components as natural drugs for the treatment of breast cancer: preliminary experiments on squalene

There is a need for the development of novel agents, which maintain the fundamental characteristics of cytoprotective drugs together with a low toxicity profile. The present study was designed to investigate the potential interest of squalene in the combinatory therapy of breast cancer with adriamycin in the breast cancer cell line MCF7. Results showed a dosage-response decrease of adriamycin on cell viability, and for all adriamycin dosages, squalene decreased or did not change viability. Squalene reduced or did not affect adriamycin apoptosis, and finally no effect of squalene was found on G0–G1 phase of the cell cycle. These results, together with previous studies, suggest that as for other natural compounds, potential anticancer effects of squalene could depend on the phenotype. Thus, there is still a need for further investigations aimed at ascertaining the real potential of squalene, using in vitro, but more importantly in vivo models.     

Increased plasma concentrations of palmitoylethanolamide, an endogenous fatty acid amide, affect oxidative damage of human low-density lipoproteins: an in vitro study

Fatty acid ethanolamides (NAEs) are naturally occurring hydrophobic molecules usually present in a very small amount in many mammalian tissues and cells. Moreover, these compounds have been isolated in mammalian biological fluids, such as blood. Palmitoylethanolamide (C16:0) (PEA) is a fully saturated NAE, which presents some possible pharmaceutical activities, such as anti-inflammatory and antinociceptive effects. PEA is physiologically present in the mammalian blood at concentrations ranging from 9.4 to 16.7 pmol/ml. Since increasing evidence indicates that oxidative modification of low-density lipoproteins (LDL) is an important determinant in atherogenesis, the aim of this study was to evaluate the effect of physiologically relevant concentrations of PEA on Cu2+-induced LDL oxidation (measured as conjugated dienes formation). Our experiments indicate both anti-oxidative and slightly pro-oxidative effects of PEA. The anti-oxidative effect is obtained at low PEA concentrations (0.01 and 0.1 microM), while the pro-oxidative effect is obtained at a higher PEA concentration (1 microM). Fluorescence and circular dichroism data indicate that the effect of PEA occurs mainly by affecting the conformational features of ApoB-100.     

Idiopathic infertility: effect of palmitoylethanolamide (a homologue of anandamide) on hyperactivated sperm cell motility and Ca2+ influx

The goal of this study was to examine the effect of palmitoylethanolamide (PEA) on the capacitation process and hyperactivated motility (HA) in idiopathic infertile men. Our data show the effect of PEA on the kinematic parameters of sperm cells from idiopathic infertile men during the capacitation of spermatozoa in vitro, both in the presence and absence of 2.5 nM PEA, a molecule physiologically present in human reproductive tracts. Two groups of sperm cells were identified. In group I (36 +/- 14 x 10(6) cells/mL), PEA significantly increased some motility parameters and HA during capacitation. In group II (58 +/- 18 x 10(6) cells/mL), PEA did not significantly modify motility parameters and HA. Fura 2 AM (acetoxymethyl ester derivative of fura 2) measurements demonstrated that PEA increased external Ca2+ influx (which modulates HA) in group I, while no change was measured in group II. In conclusion, our data indicated that PEA modulated certain physiological sperm functions that are involved in fertilization; in particular, we showed that PEA modulated for HA in men with low sperm kinematic parameters.     

Smoking-dependent effects of the angiotensin-converting enzyme gene insertion/deletion polymorphism on blood pressure

BACKGROUND: Studies on the role of the angiotensin-converting enzyme (ACE) gene in the development of hypertension have yielded conflicting results. Recent studies suggested that this gene might have smoking-dependent effects on the development of cardiovascular disease. OBJECTIVE: To study the relationship between the ACE insertion/deletion (I/D) polymorphism, blood pressure and risk of hypertension in current, former and non-smokers in a population-based cohort. METHODS: We included 2412 non-smokers, 2794 former smokers and 1508 current smokers, all participants in the Rotterdam Study. In each group, we assessed the relationship between the ACE I/D polymorphism, systolic (SBP) and diastolic (DBP) blood pressures and risk of hypertension. Mean blood pressures and prevalence of hypertension were compared between carriers and non-carriers of the D allele. All analyses were adjusted for age, sex, body mass index, diabetes mellitus, high-density lipoprotein cholesterol, total cholesterol and use of antihypertensive medication. RESULTS: In non-smokers and former smokers, blood pressure and the risk of hypertension did not differ significantly between genotypes. In smokers, we found a significant increase in SBP in DD carriers (139.6 +/- 22.8 mmHg) compared with II carriers (136.0 +/- 22.7 mmHg) (P = 0.04). No effect of ACE genotype was observed for DBP. The risk of hypertension was significantly increased in smokers who carried one [odds ratio (OR) 1.4, 95% confidence interval (CI) 1.0 to 1.9; P = 0.05] or two (OR 1.5, 95% CI 1.1 to 2.2; P = 0.02) copies of the D allele. CONCLUSIONS: The D allele of the ACE polymorphism is associated with a significantly increased SBP and risk of hypertension in smokers. Our study underlines the importance of gene-environment interactions in the study of candidate genes for hypertension.