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Biomedical subjects

A Preti

Publications and source records attributed to A Preti.

At least 19 recordsLinked to original sources

Suicide in classical mythology: cues for prevention.

OBJECTIVE: To compare well established antecedents and correlates of completed suicide with the motives and the mechanics reported in Greek mythology. METHOD: A well-known collection of Greek myths, the Book of fables by Hyginus, was explored to investigate the mechanics driving an individual to imagine, design and carry out a suicide attempt. RESULTS: Females outnumber males in the mythographer's list, their favourite methods to die being drowning, hanging, self-burning and throwing themselves down from on high. Some kind of familial recurrence of suicide was accounted for, and a large percentage of these suicides was connected to incest. Shame, sense of guilt and grief for the death of a loved one are the most frequently reported psychological correlates of the act, whereas defeat, failure or a catastrophic change in living conditions and, among females, an unfortunate love affair figure as the main antecedents of suicide. CONCLUSION: Negative life events and emotional reactions to the severing of social ties frequently occur as antecedents of suicide in Greek mythology.

Cues↗

Cytosolic sialidase Neu2 upregulation during PC12 cells differentiation.

The cytosolic sialidase Neu2 is known to be involved in myoblast differentiation. Here, we observed a Neu2 transcriptional induction during nerve growth factor, fibroblast growth factor 2 and epidermal growth factor treatments of PC12 cells, a favored model to study neuronal differentiation. The expression analysis of Neu2 deleted promoter revealed a remarkable increase of luciferase activity in treated PC12 cells, suggesting that in this cell line the Neu2 transcriptional levels are highly regulated. The enzymatic activity of cytosolic sialidase Neu2 was found to increase transiently only during differentiation, whereas was undetectable in untreated PC12 cells. These data suggest a possible involvement of cytosolic sialidase Neu2 in differentiation of PC12 cells.

Animals↗

Molecular cloning and characterization of NEU4, the fourth member of the human sialidase gene family.

Several mammalian sialidases have been cloned so far and here we describe the identification and expression of a new member of the human sialidase gene family. The NEU4 gene, identified by searching sequence databases for entries showing homologies to the human cytosolic sialidase NEU2, maps in 2q37 and encodes a 484-residue protein. The polypeptide contains all the typical sialidase amino acid motifs and, apart from an amino acid stretch that appears unique among mammalian sialidases, shows a high degree of homology for NEU2 and the plasma membrane-associated (NEU3) sialidases. RNA dot-blot analysis showed a low but wide expression pattern, with the highest level in liver. Transient transfection in COS7 cells allowed the detection of a sialidase activity toward the artificial substrate 4MU-NeuAc in the acidic range of pH. Immunofluorescence staining and Western blot analysis demonstrated the association of NEU4 with the inner cell membranes.

Amino Acid Sequence↗

Overexpression of cytosolic sialidase Neu2 induces myoblast differentiation in C2C12 cells.

Cytosolic sialidase Neu2 has been implicated in myoblast differentiation. Here we observed a significant upregulation of Neu2 expression during differentiation of murine C2C12 myoblasts. This was evidenced both as an increase in Neu2 mRNA steady-state levels and in the cytosolic sialidase enzymatic activity. To understand the biological significance of Neu2 upregulation in myoblast differentiation, C2C12 cells were stably transfected with the rat cytosolic sialidase Neu2 cDNA. Neu2 overexpressing clones were characterized by a marked decrement of cell proliferation and by the capacity to undergo spontaneous myoblast differentiation also when maintained under standard growth conditions. This was evidenced by the formation of myogenin-positive myotubes and by a significant decrease in the nuclear levels of cyclin D1 protein. No differentiation was on the contrary observed in parental and mock-transfected cells under the same experimental conditions. The results indicate that Neu2 upregulation per se is sufficient to trigger myoblast differentiation in C2C12 cells.

Animals↗

Eating disorders and aggressiveness among adolescents.

OBJECTIVE: To explore the links between propensity to aggression and eating disorders in a sample of school-aged adolescents in a northeastern area of Italy. METHOD: In a mixed male-female sample of 1000 adolescents (10% of the district's population aged 15-19 years) we administered the Eating Attitudes Test, the Bulimic Investigatory Test of Edinburgh and the Body Attitudes Test, as measures of abnormal eating attitudes and behaviours, and the Aggression Questionnaire, as a measure of the propensity to aggression. RESULTS: Females scored significantly higher than males at all eating disorders inventories (P < 0.0001). Males scored higher than females at the Aggression Questionnaire. In both genders, there was a positive correlation between scores at any of the eating disorders inventories and those at the Aggression Questionnaire (P < 0.0001). CONCLUSION: Overtly expressed aggression might have a negative impact on the course of eating disorders and on the compliance with treatment, also enhancing the risk of suicide.

Adolescent↗

Deaths by unintentional illicit drug overdose in Italy, 1984-2000.

AIM: To determine whether there has been an increase in deaths by overdose in Italy, as elsewhere in the Western world, over the past fifteen years. METHOD: This study's conclusions are based on analysis of official data on overdose deaths attributed to illicit drug addiction and abuse (ICD-9 codes 304 and 305) from 1984 to 2000, drawn from two archives of drug abuse information: the Direzione Centrale per i Servizi Antidroga (DADE) of the Italian Ministry of the Interior (1984-2000), and the Health Statistics held at the Italian Central Statistics Institute (ISTAT) (1984-1997). Mortality rates have been calculated for both genders in the following age groups: 15-24, 25-34, and 35-44 years. RESULTS: Official data indicate that there has been a steady increase in the number of deaths by overdose in Italy over recent 15 years. This trend has affected both genders, but is more evident among males. Over the whole period females had consistently lower overdose rates than males. In both genders the age group 35-44 was subject to the highest mortality rate increase over the study period, however, the highest overdose rates for both males and females were observed in the 25-34 age group. Consistently higher rates were witnessed in the northern regions of Italy with an overall increase across all latitudes. However, the greatest increase over the study period occurred in the South. In 5190 cases evaluated by the Italian Forensic Toxicology Group, 95.9% of deaths were attributed to heroin, but in about half of these, mixtures of three or more substances (heroin, benzodiazepines, cannabinoids, cocaine, methadone) were found in the deceased at doses that were likely to have contributed to death. CONCLUSIONS: The increase observed in the rates of death by overdose is likely to be a reflection of increased use of illicit drugs in the general population. Reporting practice by forensic pathologists might explain the extent of attribution of cause of death to heroin. Drop-out from addiction treatment is a commonly observed antecedent of fatal opioid overdose, therefore, caution is required when establishing treatment protocol for patients. Interventions that aim specifically at improving patient compliance with medical and psychiatric therapies should be favoured.

Adolescent↗

Social desirability and eating disorders. A community study of an Italian school-aged sample.

OBJECTIVE: To explore the links between social desirability and eating disorders in a sample of adolescents in a north-east area of Italy. METHOD: A mixed male-female sample of 1000 school-aged adolescents, corresponding to 10% of the young population aged 15-19 years living in the district, were investigated with self-reported questionnaires, including the Eating Attitudes Test (EAT), the Bulimic Investigatory Test of Edinburgh (BITE), the Body Attitudes Questionnaire (BAT), and an Italian version of the Marlowe-Crowne Social Desirability Scale (MC-SDS). RESULTS: Females scored higher than males at all eating disorder inventories. In both genders there was a negative relationship (in all cases P < 0.01) between scores at the eating disorder inventories and those at the MC-SDS. When analysing eating disorder "caseness", as measured by cut-off, "cases" reported significantly lower scores than "non-cases" at the MC-SDS in both genders. CONCLUSION: Personality traits measured by the MC-SDS, such as defensiveness, self-esteem, and dependence from approval, might contribute to the development of abnormal eating patterns at risk of eating disorders.

Adolescent↗

Metabolic fate of extracellular NAD in human skin fibroblasts.

Extracellular NAD is degraded to pyridine and purine metabolites by different types of surface-located enzymes which are expressed differently on the plasmamembrane of various human cells and tissues. In a previous report, we demonstrated that NAD-glycohydrolase, nucleotide pyrophosphatase and 5'-nucleotidase are located on the outer surface of human skin fibroblasts. Nucleotide pyrophosphatase cleaves NAD to nicotinamide mononucleotide and AMP, and 5'-nucleotidase hydrolyses AMP to adenosine. Cells incubated with NAD, produce nicotinamide, nicotinamide mononucleotide, hypoxanthine and adenine. The absence of ADPribose and adenosine in the extracellular compartment could be due to further catabolism and/or uptake of these products. To clarify the fate of the purine moiety of exogenous NAD, we investigated uptake of the products of NAD hydrolysis using U-[(14)C]-adenine-NAD. ATP was found to be the main labeled intracellular product of exogenous NAD catabolism; ADP, AMP, inosine and adenosine were also detected but in small quantities. Addition of ADPribose or adenosine to the incubation medium decreased uptake of radioactive purine, which, on the contrary, was unaffected by addition of inosine. ADPribose strongly inhibited the activity of ecto-NAD-hydrolyzing enzymes, whereas adenosine did not. Radioactive uptake by purine drastically dropped in fibroblasts incubated with (14)C-NAD and dipyridamole, an inhibitor of adenosine transport. Partial inhibition of [(14)C]-NAD uptake observed in fibroblasts depleted of ATP showed that the transport system requires ATP to some extent. All these findings suggest that adenosine is the purine form taken up by cells, and this hypothesis was confirmed incubating cultured fibroblasts with (14)C-adenosine and analyzing nucleoside uptake and intracellular metabolism under different experimental conditions. Fibroblasts incubated with [(14)C]-adenosine yield the same radioactive products as with [(14)C]-NAD; the absence of inhibition of [(14)C]-adenosine uptake by ADPribose in the presence of alpha-beta methyleneADP, an inhibitor of 5' nucleotidase, demonstrates that ADPribose coming from NAD via NAD-glycohydrolase is finally catabolised to adenosine. These results confirm that adenosine is the NAD hydrolysis product incorporated by cells and further metabolized to ATP, and that adenosine transport is partially ATP dependent.

Adenosine Triphosphate↗

Diurnal variations in suicide by age and gender in Italy.

BACKGROUND: Recent Italian statistics on suicide distribution by time of day also report data on gender and age of victims, factors which have been shown to influence the seasonal distribution of suicide and which could also affect the influence of biological circadian rhythms on suicidal behaviour. This study aims to identify and evaluate any diurnal variations that may be present in suicide occurrence by age and gender in Italy, considering data from 1994 to 1997. METHODS: The null hypothesis that there are no variations in the distribution of suicides by time of day (or over the three major periods of the day: morning, afternoon, evening/night) was tested with the chi2 goodness-of-fit test and with ANOVA. RESULTS: A clear diurnal variation in the distribution of suicides over time can be observed for both genders, with a peak in the late morning (08:00-11:00 h), and a subsequent decrease to a trough in the night hours. This trend varies with age for both genders: in particular, the age groups 45-64 and 65+ show a clear suicide peak in the morning (08:00-11:00 h), whereas younger people have a peak number of suicides in the late afternoon (16:00-19:00 h). Adults (25-44 years old) show an intermediate trend, with a less pronounced peak between the morning and early afternoon hours. The observed trend is more marked among males; however, the distribution of suicides by time of day is clearly congruent by age between both genders. CONCLUSIONS: Diurnal variation in suicide occurrence by age group may be affected by factors distributed unevenly across age groups. In particular, age distribution of disorders leading to suicidal ideation, and the sensitivity of biological systems of different age groups to environmental cues may affect each group's risk of suicide. Socio-relational factors are also likely to contribute to diurnal variation in suicide risk by age and gender. Children and adolescents can generally be presumed to be at school during the morning, therefore their opportunity for self-harm is restricted to afternoon hours. The elderly, on the other hand, may find themselves alone in the morning, when family and friends spend more time away from home due to daily work activities. LIMITATIONS: Data are based on time of death and not on presumed time of the suicidal act. For suicides committed by certain methods (e.g., poisoning) there may be a considerable difference between time of act and time of death. CLINICAL RELEVANCE: The existence of a temporal window in suicide risk implies an improvement in the surveillance of people at risk of suicide and greater attention to chronobiological factors affecting those suffering from mental disorders leading to suicide ideation.

Adolescent↗

Musical creativity and suicide.

The different abilities involved in artistic creativity may be mirrored by differences among mental disorders prevalent in each artistic profession, taking poets, painters, and composers as examples. Using suicide rates as a proxy for the prevalence of mental disorders in groups of artists, we investigated the percentage of deaths by suicide in a sample of 4,564 eminent artists who died in the 19th and 20th centuries. Of the sample, 2,259 were primarily involved in activities of a linguistic nature, e.g., poets and writers; 834 were primarily visual artists, such as painters and sculptors; and 1,471 were musicians (composers and instrumentalists). There were 63 suicides in the sample (1.3% of total deaths). Musicians as a group had lower suicide rates than literary and visual artists. Beyond socioeconomic reasons, which might favour interpretations based on effects of health selection, the lower rate of suicides among musicians may reflect some protective effect arising from music.

Art↗

CRF antagonists Dupont.

DuPont (formerly DuPont Merck), Neurocrine Biosciences and Cephalon are conducting a joint investigation into corticotropin releasingfactor (CRF) ligands. These compounds may have potential as antidepressants and anxiolytics. SV-030 and other analogs from the series are entering preclinical development [361291], [362064].

Animals↗

Risk for obstetric complications and schizophrenia.

The goal of this study was to determine whether cases with schizophrenia or related disorders show a history of obstetric complications significantly more often than control subjects and, if so, whether the enhanced risk of a negative pregnancy outcome also extends to the non-schizophrenic offspring of cases. Data based on the obstetric birth case-notes of patients with diagnosed schizophrenia or related disorders were compared to those of normal 'healthy' control subjects; each case/control pair was individually matched by gender, time and parity of birth, maternal age and marital status. Forty-four case/control pairs born in Padova (Italy) between 1964 and 1978 were assessed for prenatal and perinatal complications, including abnormal gestational age or birthweight. No significant differences were observed between cases and control subjects in the general characteristics of birth; gestational age and birthweight in particular were strictly comparable between cases and control subjects. The schizophrenia spectrum patients (75%) were more likely than control subjects (59%) to have experienced at least one definite obstetric complication: odds ratio=2.07 (95% CI: 0.83-5. 15). Cases also suffered more complications per birth than control subjects (average 2:1). In particular, obstetric complications involving a clear damaging potential were seen significantly more often among cases than control subjects: 34% vs. 9%, Fisher's exact test, P=0.008 (odds ratio=5.17, 95% CI: 1.55-17.21). Moreover, severe obstetric complications were noted more often among males (n=13, 41%) than females (n=2, 15%). When any previous pregnancies of the mothers of patients were compared with those of the mothers of control subjects, mothers of cases were seen to have suffered unfavorable pregnancy outcomes significantly more often. In particular mothers of cases were seen to have had more miscarriages (OR=4.66), and pre-term births (OR=2.58) than control subects' mothers. Severe, brain-damaging obstetric complications would seem to be a possible antecedent to a diagnosis of schizophrenia or a related disorder in adulthood. Indeed, some early onset cases may be accounted for by prenatal brain lesions. This enhanced risk of negative pregnancy outcome may be under genetic control, contributing to the persistence of schizophrenia in the general population. The 'healthy' status of control subjects was ascertained indirectly, not by individual assessment of the subjects. The sample size limits the statistical power of calculations.

Adult↗

Identification and expression of NEU3, a novel human sialidase associated to the plasma membrane.

Several mammalian sialidases have been described so far, suggesting the existence of numerous polypeptides with different tissue distributions, subcellular localizations and substrate specificities. Among these enzymes, plasma-membrane-associated sialidase(s) have a pivotal role in modulating the ganglioside content of the lipid bilayer, suggesting their involvement in the complex mechanisms governing cell-surface biological functions. Here we describe the identification and expression of a human plasma-membrane-associated sialidase, NEU3, isolated starting from an expressed sequence tag (EST) clone. The cDNA for this sialidase encodes a 428-residue protein containing a putative transmembrane helix, a YRIP (single-letter amino acid codes) motif and three Asp boxes characteristic of sialidases. The polypeptide shows high sequence identity (78%) with the membrane-associated sialidase recently purified and cloned from Bos taurus. Northern blot analysis showed a wide pattern of expression of the gene, in both adult and fetal human tissues. Transient expression in COS7 cells permitted the detection of a sialidase activity with high activity towards ganglioside substrates at a pH optimum of 3.8. Immunofluorescence staining of the transfected COS7 cells demonstrated the protein's localization in the plasma membrane.

Alternative Splicing↗

Increase in first admissions for schizophrenia and other major psychoses in Italy.

Despite reports of falling first-admission rates for schizophrenia in some Western countries, methodological problems and bias preclude a definite conclusion about a genuine fall in the incidence of schizophrenia. This study set out to test the hypothesis that first admissions for schizophrenia in Italy have fallen in recent years. All admissions rated as 'first contact' in Italy from 1984 to 1994 for severe mental illnesses to general hospital psychiatric services, as reported in the Italian National Institute for Statistics Health-Care Yearbooks, were considered. Data were analyzed as rates per 100000 in the general population, and changes over time in incidence of schizophrenia, paranoia, affective psychoses and drug-induced psychoses (diagnosed according to ICD 9) were recorded. Changes in rates over time, with rates as the dependent variable and years as the independent variable, were the main outcome measure. First-admission rates for schizophrenia and paranoia increased progressively from 1984 to 1994, as did those for affective psychoses, mania and, to a lesser extent, major depression. In the same period, all admissions (both total and rated as 'first-contact') for mental disorders increased. Although linear regression tests for admission rates in most, but not all, cases indicate a significant ascending linear trend, quadratic model results show a significantly better fit than does the simple linear regression model for the majority of data. The change described by the quadratic model suggests an increase in admission rates more marked in the second half than in the first half of the period of the study. First-admission rates for schizophrenia and, to a lesser extent, paranoia seemed to increase concurrent to a decrease in first-admission rates for 'other' non-organic psychoses. Contrary to reports from other Western countries, hospital incidence in Italy for schizophrenia is on the increase, as is that for other severe psychoses. This increase is likely to be a reflection of changes in mental health-care organisation, in treatment and diagnostic patterns, and in cultural attitudes towards mental illness. Radical changes in the true incidence of psychoses, in particular of mood disorders, as described elsewhere, cannot be ruled out as contributing factors. Data bias and limitations preclude a generalisation of results, however.

Adolescent↗

Nerve growth factor induces sphingomyelin accumulation in pheochromocytoma cells.

The pheochromocytoma cells are a well-known model for studying the nerve growth factor (NGF)-induced molecular changes during the differentiation process. The involvement of sphingomyelin (SM) was studied using the fluorescent analogue of ceramide, i.e. N-lissamine rhodaminyl-(12-aminododecanoyl) D-erythro-sphingosine (C12-LRh-Cer). This fluorescent analogue is metabolically active and can be used to follow the biosynthesis of SM in intact cells. NGF induces a 4-fold increase of fluorescent SM content in PC12 cells, when loaded with C12-LRh-Cer. Treatment of PC12 cells with actinomycin D or cycloheximide completely abolishes the NGF-induced elevation of SM. Inhibition of p140(trkA) receptor by AG-879 prevents extracellular signal-regulated kinase 1/2 phosphorylation and suppresses the increase of SM. Inhibition of protein kinase C (PKC), protein kinase A (PKA) and phosphatidylinositol 3-kinase does not have any effect on NGF-induced C12-LRh-SM accumulation. On the other hand, activation of PKA or PKC with simultaneous treatment with NGF has a synergistic effect on increase of SM content. The NGF-induced SM increase in PC12 cells is an effect promoted by other differentiating agents like dibutyryl cyclic AMP or fibroblast growth factor-2 but not by a mitogenic agent like epidermal growth factor.

Animals↗

Obstetric complications in patients with depression--a population-based case-control study.

BACKGROUND: To examine whether sufferers of affective disorders are more likely to be subject to obstetric complications than normal healthy people. METHOD: Data based on prospectively recorded birth case-notes for patients with a diagnosis of depression (or related disorders) with early onset were compared to those of normal healthy controls, individually matched by gender, time and parity of birth, maternal age and marital status. RESULTS: Forty-one case-controls pairs born between 1964 and 1978 were compared. No differences between cases and controls in gestational age or birthweight were significant, though depressive patients on average weighed 200 g less than controls at birth. Patients were more likely than controls to be small for their gestational age (22 vs. 1: chi(2)=4.34, P=0.03). They were significantly more likely than controls to have suffered at least one obstetric complication: 35 (85%) vs. 25 (60%), chi(2)=5.03, P=0.02; or more than one (two on average, as opposed to one on average among controls). No obstetric complication was seen significantly more among cases than controls, apart from bleeding during gestation, which was observed for four cases and no controls. The prevalence of complications with a clear brain damaging potential did not differ significantly between cases and controls: 11 (26%) vs. 8 (19%). CONCLUSIONS: A developmental deficit, as indicated by lower birthweight and gestational age, may contribute to the risk of depressive breakdowns and affective disorders in later life. Severe, brain damaging obstetric complications are unlikely to be a significant risk factor for affective disorders, though some early onset cases may be accounted for by prenatal brain lesions. LIMITATIONS: Sample size limits statistical power for isolation of a rare, single risk factor.

Adult↗