Marco Bertona

Raised plasma nerve growth factor levels associated with early-stage romantic love.

Our current knowledge of the neurobiology of romantic love remains scanty. In view of the complexity of a sentiment like love, it would not be surprising that a diversity of biochemical mechanisms could be involved in the mood changes of the initial stage of a romance. In the present study, we have examined whether the early romantic phase of a loving relationship could be associated with alterations in circulating levels of neurotrophins (NTs). Plasma levels of NGF, BDNF, NT-3 and NT-4 were measured in a total of 58 subjects who had recently fallen in love and compared with those of two control groups, consisting of subjects who were either single or were already engaged in a long-lasting relationship. NGF level was significantly higher (p < 0.001) in the subjects in love [mean (SEM): 227 (14) pg/ml] than in either the subjects with a long-lasting relationship [123 (10) pg/ml] or the subjects with no relationship [149 (12) pg/ml]. Notably, there was also a significant positive correlation between levels of NGF and the intensity of romantic love as assessed with the passionate love scale (r = 0.34; p = 0.007). No differences in the concentrations of other NTs were detected. In 39 subjects in love who-after 12-24 months-maintained the same relationship but were no longer in the same mental state to which they had referred during the initial evaluation, plasma NGF levels decreased and became indistinguishable from those of the control groups. Taken together, these findings suggest that some behavioural and/or psychological features associated with falling in love could be related to raised NGF levels in the bloodstream.

The T393C polymorphism of the GNAS1 gene is associated with deficit schizophrenia in an Italian population sample

Programmed cell death and alterations in intracellular G-protein signaling may be involved in the pathophysiology of schizophrenia. The Galphas subunit of heterotrimeric G-proteins, encoded by the gene GNAS1, may play a role in both of these processes. Additionally, transgenic mice expressing a constitutively active form of Galphas provide a reliable model of certain endophenotypes of schizophrenia. To investigate whether the functional single nucleotide polymorphism T393C in GNAS1 gene could affect risk of schizophrenia, we examined its distribution in Italian subjects with (n=383) and without (n=400) schizophrenia. We also evaluated whether a specific association could exist between the deficit (n=108) and nondeficit (n=275) forms of the disorder. The alleles and genotypes frequency in the entire cohort of schizophrenic patients did not differ from that of controls. However, the frequency of the homozygous 393TT genotype was significantly higher in deficit schizophrenic patients (37.1%) compared to both nondeficit schizophrenic (22.5%, p=0.011) and controls (22.8%, p=0.015). This association with deficit schizophrenia persisted even after allowance for potential confounders [adjusted odds ratio (OR) for deficit schizophrenia: 2.06 (95% confidence interval (CI): 1.21-3.47), p=0.007]. Altogether, our data suggest that the GNAS1 T393C status could influence susceptibility for deficit schizophrenia in Italian subjects.

A multilocus candidate approach identifies ACE and HIF1A as susceptibility genes for cellulite.

Background  Cellulite is a common complex cosmetic problem for many post‐adolescent women characterised by relief alterations of the skin surface, which give the skin an orange‐peel appearance. Although genetic factors have been suggested to play a role in the development of cellulite, the genetic background of this condition remains unclear. We therefore conducted a multi‐locus genetic study examining the potential associations of candidate gene variants in oestrogen receptors, endothelial function/adipose tissue hypoxia, lipid metabolism, extracellular matrix homeostasis, inflammation and adipose tissue biology, with the risk of cellulite.

Serum levels of vascular endothelial growth factor and its receptors in patients with severe autism

OBJECTIVE To study vascular endothelial growth factor (VEGF) and its soluble receptors sVEGFR-1 and -2 in autism. DESIGN AND METHODS We measured serum levels of angiogenic molecules in 22 patients with severe autism and 28 controls. RESULTS Patients and controls had similar sVEGFR-2 levels, but VEGF levels were lower and sVEGFR-1 higher in patients with autism. CONCLUSION The imbalance between VEGF and its receptor sVEGFR-1 may be involved in the pathophysiology of autism.

Reduced ultraviolet-induced DNA damage and apoptosis in human skin with topical application of a photolyase-containing DNA repair enzyme cream: Clues to skin cancer prevention

The exposure of human skin to ultraviolet radiation (UVR) results in the formation of DNA photolesions that give rise to photoaging, mutations, cell death and the onset of carcinogenic events. Photolyase (EC 4.1.99.3) is a DNA repair enzyme that reverses damage caused by exposure to UVR. We sought to investigate whether addition of photolyase enhances the protection provided by a traditional sunscreen (SS), by reducing the in vivo formation of cyclobutane-type pyrimidine dimers (CPDs) and UVR-induced apoptosis in human skin. Ten volunteers (Fitzpatrick skin type II) were exposed to solar-simulated (ss) UVR at a three times minimal erythema dose for 4 consecutive days. Thirty minutes prior to each exposure, the test materials [vehicle, SS (sun protection factor 50) alone, and SS plus photolyase from Anacystis nidulans] were applied topically to three different sites. One additional site was left untreated and one received ssUVR only. Biopsy specimens were taken 72 h after the last irradiation. The amount of CPDs and the extent of apoptosis were measured by ELISA. Photolyase plus SS was superior to SS alone in reducing both the formation of CPDs and apoptotic cell death (both P<0.001). In conclusion, the addition of photolyase to a traditional SS contributes significantly to the prevention of UVR-induced DNA damage and apoptosis when applied topically to human skin.

Genetic association of alpha2-Heremans–Schmid glycoprotein polymorphism with late-onset Alzheimer's disease in Italians

Alpha2-Heremans-Schmid glycoprotein (AHSG), also known as fetuin-A, is a highly glycosylated protein which has been recently reported to be decreased in the cerebrospinal fluid of patients with Alzheimers disease. AHSG is genetically polymorphic and two common alleles, AHSG*1 and AHSG*2, have been described. The purpose of this study was to investigate the distribution of AHSG gene polymorphism in 235 Caucasian Italian patients with late-onset Alzheimers disease (LOAD) and 235 age- and gender-matched healthy controls. In patients with LOAD, the genotype distribution was 184 AHSG 1*1, 44 AHSG 1*2, 7 AHSG 2*2, and was significantly different from that observed in the 235 control subjects (117 AHSG 1*1, 103 AHSG 1*2, 15 AHSG 2*2) (chi(2)=41.50, P<0.0001). After allowance for age, gender and APOE epsilon4 status, multivariate logistic regression analysis revealed that the adjusted odds ratio for the development of LOAD in AHSG 1*1 homozygotes was 3.90 (95% CI: 2.58-5.90, P<0.0001). These results suggest that the AHSG gene polymorphism may be associated with LOAD in Italians. Additional studies are warranted to examine the biological relevance of AHSG in the pathophysiology of neurodegenerative disorders.

Serum omega-3 fatty acids are associated with ultimatum bargaining behavior

In the ultimatum game (UG), two players are involved to bargain over a division of a given sum of money. The proposer makes an ultimatum offer of a fraction of money, while the responder can either accept or reject the proposers decision. In case of rejection of the proposed splitting by the responder, neither player gets anything. Adverse psychological reactions are deemed to play a role in the rejection of unfair offers. Low serum levels of omega-3 polyunsaturated fatty acids have been linked to impulse control and hostility. This study examined the serum omega-3 and omega-6 fractions in relation to the ultimatum bargaining behavior. Participants were sixty economy students (31 males and 29 females, mean age: 24.4+/-2.3 years) who played a euro 10 ultimatum game. Ultimatum offers were constrained to be euro 5 (proposer keeps euro 5) or euro 1 (proposer keeps euro 9) to generate a roughly even split between fair (5:5) and unfair (1:9) offers. Fasting serum alpha-linolenic (ALA), eicosapentaenoic (EPA), docosahexaenoic acid (DHA), linoleic acid (LA) and arachidonic acid (AA) were assayed with gas chromatography. In participants who rejected unfair offers there was a significant depletion of ALA, EPA and DHA. Moreover, the ratio of serum omega-3/omega-6 fatty acids was significantly lower in patients who rejected unfair offers as compared to those who did not. The results of this study suggest that a depletion of the serum omega-3 fatty acids is associated with rejections of unfair ultimatum offers in an experimental neuroeconomic setting.

Anti-inflammatory effects of a topical preparation containing nicotinamide, retinol, and 7-dehydrocholesterol in patients with acne: a gene expression study

Purpose Acne vulgaris is a skin disorder of the sebaceous follicles, involving hyperkeratinization and perifollicular inflammation. Aberrant extracellular matrix remodeling due to matrix metalloproteinases (MMPs) has been associated with the presence of acne conditions. Given the complex pathophysiology of acne, novel topical therapies should include combination products that target multiple pathogenetic mechanisms. In this pilot study we investigated the changes in gene expression of extracellular MMPs, the tissue inhibitors of metalloproteinases, and proinflammatory molecules after 45 days of topical application of a combination product containing nicotinamide, retinol, and 7-dehydrocholesterol in 16 patients with inflammatory acne on their back. Materials and methods Skin biopsies were obtained before and after treatment for gene expression studies. Results Quantitative real-time polymerase chain reaction revealed a significant downregulation of MMP-1, MMP-2, MMP-9, MMP-14, interleukin-6, monocyte chemoattractant protein-1, and macrophage migration inhibitory factor. In contrast, the tissue inhibitors of metalloproteinases and transforming growth factor-β1 were significantly upregulated. The gene expression findings correlated well with the clinical treatment response. Conclusions The combination of nicotinamide, retinol, and 7-dehydrocholesterol appears to be effective for acne treatment from both clinical and molecular standpoints.

The M694V Variant of the Familial Mediterranean Fever Gene Is Associated with Sporadic Early-Onset Alzheimer’s Disease in an Italian Population Sample

Background: Inflammation is deemed to play a crucial role in the pathogenesis of Alzheimer’s disease (AD). We sought to determine whether the proinflammatory M694V mutation of pyrin, the gene responsible for familial Mediterranean fever, could lead to an increased risk for AD. Methods: We compared the M694V variant genotypes in 378 sporadic AD patients and 384 healthy control subjects of Italian descent. Results: After adjustment for potential confounders, the M694V mutation was found to be associated with an increased risk for AD in subjects with an age at onset of 65 years or younger (multivariate-adjusted odds ratio, OR: 3.01, 95% confidence interval, CI: 1.24–6.72, p = 0.021), but not in patients with an age at onset older than 65 years (multivariate-adjusted OR: 0.81, 95% CI: 0.34–1.99, p = 0.847). Kaplan-Meier analysis indicated that AD patients bearing the M694V mutation presented with disease onset 7 years earlier than carriers of the wild-type genotype (log rank = 41.61, p < 0.001). Conclusion: Our data indicate that the M694V sequence variant in the pyrin gene might influence the age at onset of AD in the Italian population.