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Biomedical subjects

M Maj

Publications and source records attributed to M Maj.

At least 19 recordsLinked to original sources
PubMed2006

Family burden and social network in schizophrenia vs. physical diseases: preliminary results from an Italian national study.

OBJECTIVE: To compare burden and social network in families of patients with schizophrenia or physical diseases. METHOD: A total of 709 relatives of patients with schizophrenia and 646 relatives of patients with physical diseases were recruited in 169 specialized units located in 30 randomly selected Italian geographical areas. RESULTS: In both groups, the consequences of caregiving most frequently reported as present were constraints in social activities, negative effects on family life and a feeling of loss. Objective burden was similar in the two groups, while subjective burden was higher in schizophrenia. Social support was lower among relatives of patients with schizophrenia than among those of the other group. CONCLUSION: These results highlight the need to provide families of those with long-term diseases with supportive interventions, aiming to: i) manage relatives' psychological reactions to patient's illness; ii) provide information on patient's disease; iii) reinforce relatives' social network, especially in the case of schizophrenia.

Adolescent↗
PubMed2004

Interleukin-1beta and tumor necrosis factor-alpha in children with major depressive disorder or dysthymia.

BACKGROUND: Immune function is altered in adult depressed patients. The aim of our study was to see whether or not cytokine secretion is impaired at a very young phase of development of depressive disorders, possibly being pathogenetically involved in their course. METHODS: Basal plasma concentrations of interleukin-1beta (Il-1beta) and tumor necrosis factor-alpha (TNF-alpha) were measured radioimmunologically in 22 drug-free children-adolescents, 11 with recurrent major depressive disorders (MDD) and 11 with dysthymia (DYS), and in 11 psychophysically healthy age-sex matched controls. Depression was monitored using the Poznanski Rating Scale and Anxiety with the Reynold Rating Scale. RESULTS: Il-1beta levels were not significantly different in MDD from controls and significantly higher than normal in DYS subjects. TNF-alpha levels were not significantly different in MDD patients from controls and significantly lower than normal in DYS patients. Cytokine concentrations were correlated with anxious and depressive symptomatology in MDD but not in DYS patients. CONCLUSIONS: There is a cytokine pathology in depressive disorders of obscure etiopathogenetical significance.

Adolescent↗
PubMed2004

Intestinal permeability is decreased in anorexia nervosa.

Malnutrition and absence of exogenous luminal nutrients in the gastrointestinal tract affect intestinal permeability (IP) leading to an increased penetration of substances that passively cross intestinal epithelium via intercellular pathways. We hypothesised that an increase in IP could occur in patients with anorexia nervosa because of their prolonged fasting and chronic malnutrition. Therefore, we assessed IP in 14 drug-free anorexic women and 19 drug-free age-matched healthy women by means of the lactulose/mannitol (LA/MA) test. To this purpose, after an overnight fast, subjects ingested an oral solution containing 5 g lactulose and 2 g mannitol in 100 ml water. Urine specimens were collected immediately before and 30, 60, 120, 180, 240 and 300 min after the ingestion of the sugar solution. Urinary lactulose and mannitol were determined by high-performance anion exchange chromatography coupled with pulsed amperometric detection. We found that IP, as expressed by the 5-h LA/MA excretion ratio, was significantly decreased in anorexic women because of a lower urinary recovery of lactulose. Moreover, in patients, the time course of lactulose excretion significantly differs from healthy controls. These results do not confirm our hypothesis of increased IP in anorexia nervosa. Since IP reflects the anatomo-functional status of intestinal mucosa, the present findings support the idea that changes in the anatomo-physiology of intestinal mucosa occur in anorexia nervosa.

Adult↗
PubMed2004

Synthesis of new hexahydro- and octahydropyrido[1,2-c]pyrimidine derivatives with an arylpiperazine moiety as ligands for 5-HT(1A) and 5-HT(2A) receptors, Part 2.

The synthesis of new of 4-aryl-hexahydro- (11-16) and (R,R)(S,S)4-aryl-octahydropyrido[1,2-c]pyrimidine (23-27) derivatives bearing a aryl- or heteroarylpiperazinyl moiety in position 2 is described. The derivatives of 4-aryl-hexahydro- (1-5) and (R,R)(S,S)4-aryl-octahydropyrido[1,2-c]pyrimidin-1,3-dion (17-19) served as starting compounds for further synteses. The N-alkylation of the imide moiety in compounds 1-5 and 17-19 by 1,4-dibromobutane gave the respective monbromobutyl derivatives 6-10 and 20-22. The final derivatives 11-16 and 23-27 have been produced by condensation of the obtained bromoderivatives with selected 1-aryl and 1-heteroarylpiperazines. Compounds 11-16 and 23-27 were tested for their affinity towards 5-HT(1A), 5-HT(2A) and alpha1 receptors, using a radioligand binding assay.

Animals↗
PubMed2003

(-)-PHCCC, a positive allosteric modulator of mGluR4: characterization, mechanism of action, and neuroprotection.

Group-III metabotropic glutamate receptors (mGluR4, -6, -7, and -8) modulate neurotoxicity of excitatory amino acids and beta-amyloid-peptide (betaAP), as well as epileptic convulsions, most likely via presynaptic inhibition of glutamatergic neurotransmission. Due to the lack of subtype-selective ligands for group-III receptors, we previously utilized knock-out mice to identify mGluR4 as the primary receptor mediating neuroprotection of unselective group-III agonists such as L-AP(4) or (+)-PPG, whereas mGluR7 is critical for anticonvulsive effects. In a recent effort to find group-III subtype-selective drugs we identified (+/-)-PHCCC as a positive allosteric modulator for mGluR4. This compound increases agonist potency and markedly enhances maximum efficacy and, at higher concentrations, directly activates mGluR4 with low efficacy. All the activity of (+/-)-PHCCC resides in the (-)-enantiomer, which is inactive at mGluR2, -3, -5a, -6, -7b and -8a, but shows partial antagonist activity at mGluR1b (30% maximum antagonist efficacy). Chimeric receptor studies showed that the binding site of (-)-PHCCC is localized in the transmembrane region.Finally, (-)-PHCCC showed neuroprotection against betaAP- and NMDA-toxicity in mixed cultures of mouse cortical neurons. This neuroprotection was additive to that induced by the highly efficacious mGluR1 antagonist CPCCOEt and was blocked by MSOP, a group-III mGluR antagonist. Our data provide evidence for a novel pharmacological site on mGluR4, which may be used as a target-site for therapeutics.

Amyloid beta-Peptides↗
PubMed2003

Morphine and cocaine influence on CRF biosynthesis in the rat central nucleus of amygdala.

The central nucleus of the amygdala is a CRF-containing limbic brain site which mediates both fear-like and avoidance behaviors; moreover it has been hypothesized that atypical stress responses may contribute to compulsive drug use. Therefore, we studied in rat amygdala the level of CRF mRNA by in situ hybrydization, and the level of the peptide using immunocytochemistry after acute and chronic administration of morphine and cocaine and after their withdrawal. Acute injection of morphine (20 mg/kg i.p.) increased CRF mRNA level, but did not change significantly CRF immunoreactivity in the central nucleus of the amygdala. Chronic morphine administration significantly increased the level of CRF mRNA 3, 24 and 48 h after the last dose. Both, acute and chronic cocaine administration increased CRF mRNA, but the peptide level was decreased only after acute cocaine administration. However, in the late withdrawal (48 h after the last dose of cocaine) both mRNA and the peptide levels tended to decrease. The above data suggest that amygdalar CRF system activity is potently activated after administration of morphine and cocaine, and that activation of this system observed at the time of withdrawal from morphine may be responsible for aversion and anxiety related to these states; therefore a CRF1 receptor may be a target for prospective pharmacotherapies of the withdrawal from abused drugs.

Amygdala↗
PubMed2003

Ghrelin and leptin responses to food ingestion in bulimia nervosa: implications for binge-eating and compensatory behaviours.

BACKGROUND: Ghrelin and leptin are endogenous peripheral proteins involved in the regulation of eating behaviour. In particular, ghrelin stimulates hunger and promotes food ingestion, whereas leptin increases satiety and reduces food consumption. Therefore, alterations in the physiology of these peptides may play a role in the pathogenesis of eating disorders such as bulimia nervosa. In the present study, we investigated ghrelin and leptin responses to food ingestion in patients with bulimia nervosa. METHOD: Nine symptomatic drug-free bulimic women and 12 age-matched healthy women ingested a meal of 1207 kcal (60% carbohydrates, 23% fat and 17% proteins) at 12.00 a.m. and underwent blood sample collection before and 45, 60, 90, 120 and 180 min after the meal. Plasma levels of ghrelin, leptin, insulin and glucose were measured. RESULTS: In healthy women, circulating ghrelin exhibited a drastic decrease after the food intake whereas, in bulimic patients, this response was significantly blunted. No difference between the two subjects groups was observed in post-prandial profiles of plasma leptin, insulin and glucose. CONCLUSIONS: The lack of a leptin response to food ingestion, in both bulimic and healthy women, is compatible with the role of this peptide as long-term rather than short-term modulator of eating behaviour. The blunted ghrelin response to food ingestion may support the occurrence in bulimic subjects of an impaired suppression of the drive to eat following a meal. This may have implications for binge-eating.

Adult↗
PubMed2003

Altered immunoreactive levels of G proteins in peripheral mononuclear cells of patients with anorexia nervosa and bulimia nervosa.

Alterations of cellular G proteins have been implicated in the pathophysiology of some psychiatric disorders. So far, no study assessed G protein function in anorexia nervosa (AN) and bulimia nervosa (BN). Therefore, we measured immunoreactive levels of G(alpha s), G(alpha i), G(alpha q/11) and G(beta) protein subunits in mononuclear leukocytes of 71 drug-free women, including 25 subjects with AN, 26 individuals with BN and 20 healthy controls. As compared to healthy women, anorexic patients exhibited significantly increased levels of G(alpha i) and G(beta) proteins, while bulimic patients had significantly increased levels of G(alpha s), G(alpha i) and G(beta) proteins. Immunoreactive levels of peripheral G protein subunits were not significantly correlated with demographic or nutritional parameters. These findings, although obtained in peripheral blood cells, may suggest a derangement of G protein-mediated signal transduction in the pathophysiology of eating disorders.

Adolescent↗
PubMed2002

The impact of professional and social network support on the burden of families of patients with schizophrenia in Italy.

OBJECTIVE: (a) To explore burden related to caregiving and support received from professionals and social network in relatives of patients with schizophrenia in Northern, Central and Southern Italy; and (b) to test whether a higher level of family burden is associated with a lower level of professional and social network support. METHOD: Seven hundred and nine patients with schizophrenia and their key-relatives were consecutively recruited in 30 Italian mental health departments. Data were collected on: (a) patients' clinical status and levels of disability; (b) relatives' burden, social and professional support; (c) interventions received by patients and their families. RESULTS: Family burden was found lower in Northern Italy. However, after controlling for psychosocial interventions, differences in family burden among the three geographical areas disappeared. Family burden was associated with patients' levels of disability and manic/hostility symptoms, and with professional and social network support received by the family. CONCLUSION: Professional and social network support represent crucial resources to reduce family burden in schizophrenia.

Adult↗
PubMed2002

Opposite modifications in circulating leptin and soluble leptin receptor across the eating disorder spectrum.

Leptin is thought to modulate feeding behaviour, body weight and energy metabolism by acting through specific cellular receptors. Derangements of leptin production have been repeatedly reported in patients with anorexia nervosa (AN) or bulimia nervosa (BN), but no information has been provided on the functional status of leptin receptors in these disorders. Therefore, we measured plasma levels of leptin and its soluble receptor (Ob-Re) in a total of 130 women, including 22 patients with AN, 45 patients with BN, 18 patients with the binge-eating disorder (BED), 12 non-binge eating obese women and 33 healthy women. Circulating leptin was drastically reduced in underweight anorexics and normal-weight bulimics, but increased in overweight BED patients and non-binge-eating obese women. Conversely, plasma levels of Ob-Re were significantly increased in patients with AN or BN, but decreased in BED and non-binge-eating obese women. Significant inverse correlations were detected between plasma levels of leptin and those of Ob-Re in all the subject groups, except in non-binge-eating obese subjects. These results show, for the first time, that opposite modifications occur in circulating levels of leptin and Ob-Re across the eating-disorder spectrum. The relevance of these findings to the pathophysiology and treatment of eating disorders remains to be elucidated.

Adult↗
PubMed2001

Brain electrical microstates in subjects with panic disorder.

Brain electrical microstates represent spatial configurations of scalp recorded brain electrical activity and are considered to be the basic elements of stepwise processing of information in the brain. In the present study, the hypothesis of a temporo-limbic dysfunction in panic disorder (PD) was tested by investigating the topographic descriptors of brain microstates, in particular the one corresponding to the Late Positive Complex (LPC), an event-related potential (ERP) component with generators in these regions. ERPs were recorded in PD patients and matched healthy subjects during a target detection task, in a central (CC) and a lateral condition (LC). In the CC, a leftward shift of the LPC microstate positive centroid was observed in the patients with PD versus the healthy control subjects. In the LC, the topographic descriptor of the first microstate showed a rightward shift, while those of both the second and the fourth microstate, corresponding to the LPC, revealed a leftward shift in the PD patients versus the healthy control subjects. These findings indicate an overactivation of the right hemisphere networks involved in early visual processing and a hypoactivation of the right hemisphere circuits involved in LPC generators in PD. In line with this interpretation, the abnormal topography of the LPC microstate, observed in the CC, was associated with a worse performance on a test exploring right temporo-hippocampal functioning. Topographical abnormalities found for the LPC microstate in the LC were associated with a higher number of panic attacks, suggesting a pathogenetic role of the right temporo-hippocampal dysfunction in PD.

Adult↗
PubMed2001

Diagnosis and treatment of rapidly cycling bipolar disorder.

The conceptualization of rapidly cycling bipolar disorder remains controversial. The DSM-IV definition of rapid cycling, although very reliable, may be not sufficiently inclusive (i.e., it may exclude patients with very short episodes of very high frequency, who are very typical in terms of external validators, and are currently regarded as rapid cyclers by many researchers and clinicians). Moreover, the addition of the requirement of pole switching (i.e., at least one direct transition from one polarity of mood to the other) during the previous year may increase the prognostic and treatment response implications of the diagnosis of rapid cycling. It is commonly held that rapid cyclers are refractory to lithium prophylaxis. However, currently available research evidence suggests that lithium prophylaxis does exert an impact on the course of rapidly cycling bipolar disorder. One double-blind crossover study supports the clinical impression that the combination of at least two mood stabilizers may be needed in most rapid cyclers.

Antimanic Agents↗
PubMed2001

Lower serum activity of prolyl endopeptidase in anorexia and bulimia nervosa.

The aim of this study was to examine whether anorexia and bulimia nervosa are accompanied by lower serum activity of prolyl endopeptidase (PEP;EC 3.4.21.26; post-proline cleaving enzyme), a cytosolic endopeptidase which cleaves peptide bonds on the carboxyl side of proline in proteins of relatively small molecular mass. Substrates of PEP are, amongst others, neuroactive peptides, such as arginine vasopressin, luteinizing hormone-releasing hormone, thyrotropin releasing hormone,alpha-melanocyte secreting hormone, substance P, oxytocin, bradykinin, neurotensin and angiotensin (Ag) I and II. Serum PEP activity was measured in the serum of 18 normal women, 21 anorexia nervosa and 21 bulimia nervosa women by means of a fluoremetric method. The Bulimic Investigatory Test, Edinburgh (BITE), the Eating Disorder Inventory (EDI) and the Hamilton Depression Rating Scale (HDRS) were scored. Serum PEP activity was significantly lower in patients with bulimia nervosa and anorexia nervosa, irrespective of the restricted or binging subtype, than in normal controls. There were significant and inverse correlations between serum PEP activity and the HDRS and BITE. In anorectic patients, but not in normal or bulimic patients, there was a significant correlation between serum PEP and body mass index. In bulimic patients, but not in normal or anorectic patients, there was a significant correlation between serum PEP and duration of illness. It is concluded that lowered serum PEP activity takes part in the pathophysiology of anorexia and bulimia nervosa. It is hypothesized that a combined dysregulation of PEP and neuroactive peptides, which are substrates of PEP, could be an integral component of eating disorders.

Adult↗
PubMed2001

Psychological consequences of the 1998 landslide in Sarno, Italy: a community study.

OBJECTIVE: This community study assessed the prevalence of post-traumatic stress disorder (PTSD) and the psychosocial consequences of the landslide which occurred in Sarno, Southern Italy, in May 1998. METHOD: A random sample (n=272) of the population living in the highest risk area of Sarno, and a control group recruited in a small town situated near the disaster area, but not affected by the event, were assessed 1 year after the disaster by standardized instruments. RESULTS: Of the subjects recruited in Sarno, 27.6% met DSM-IV criteria for PTSD; 59% subjects recruited in Sarno and 35% of the control group were identified as "probable cases" by the GHQ-30 (P<0.0001). Subjects recruited in Sarno had significantly higher scores on the four GHQ-30 subscales identified by factor analysis. CONCLUSION: This study emphasizes the negative impact of a natural catastrophic event on mental health, and the need for preventive interventions.

Adolescent↗
PubMed2001

Pharmacological studies on the monoaminergic influence on the synthesis and expression of neuropeptide Y and corticotropin releasing factor in rat brain amygdala.

Our earlier findings concerning the 6-OHDA lesion suggested dopaminergic regulation of neuropeptide Y (NPY) and corticotropin releasing factor (CRF) synthesis and expression in amygdala neurons. On the other hand, some other studies indicated that not only dopamine, but also other monoamines may modulate peptidergic neurons. Therefore the present study examined the effect of pharmacological deprivation of monoaminergic influences on NPY and CRF neurons in rat brain amygdala by means of in situ hybridization and immunohistochemical methods. It was found that NPY mRNA expression in the amygdala decreased after 24h blockade of dopaminergic D1 and D2 receptors, by haloperidol or SCH23390. At the same time the NPY-peptide expression measured immunohistochemically was not significantly changed. A prolonged, 14-day, blockade of dopaminergic receptors by haloperidol induced an opposite effect, an increase in NPY mRNA expression. Impairment of the serotonergic transmission by blockade of 5-HT synthesis using p-chlorophenylalanine, as well as attenuation of the noradrenergic transmission by NA depletion from terminals by DSP4, did not significantly change NPY mRNA expression or the mean number of NPY-immunoreactive neurons in the amygdala. Only a decrease in the staining intensity observed as a decreased number of darkly stained neurons was found after both compounds. Neither the dopamine receptor blockade nor the impairment of serotonergic or noradrenergic transmission changed CRF mRNA or the peptide expression in the amygdala. The obtained results indicate that in rat brain amygdala, of all the monoamines, dopamine seems to be the most important modulator of NPY biosynthesis and expression. The effect of blockade of dopaminergic receptors is biphasic: first it induces a decrease and then - after prolonged treatment an increase in NPY mRNA. Serotonergic and noradrenergic systems in the amygdala seem to be connected with regulation of NPY release rather than the biosynthesis.

Amygdala↗
PubMed2001

Plasma concentrations of amino acids in chronic schizophrenics treated with clozapine.

Peripheral amino acid changes have been reported in schizophrenia, but results are not consistent. We measured serum levels of different amino acids in 11 neuroleptic-resistant schizophrenic patients before and after clozapine treatment and in 11 age- and sex-matched healthy subjects. The schizophrenic patients exhibited significantly higher levels of serum aspartate, glutamate, isoleucine, histidine and tyrosine and significantly lower concentrations of serum asparagine, tryptophan and serine. In patients, the ratio between tryptophan and large neutral amino acids (LNAA) was significantly lower than in matched controls, whereas the tyrosine/LNAA ratio did not differ significantly. Moreover, 12 weeks of clozapine administration significantly reduced serum levels of glutamate but did not restore the values observed in normal controls, nor did it affect other amino acid concentrations. These data show changes in serum amino acids that may influence central serotonergic, dopaminergic and glutamatergic transmission in neuroleptic-resistant schizophrenics.

Adult↗
PubMed2001

A multicenter Italian study of patients' relatives' beliefs about schizophrenia.

This study explored patients' relatives' beliefs about schizophrenia in Italy, a country with a long history of community-based psychiatry. The study was conducted among 709 key relatives of patients with schizophrenia who were recruited in 30 mental health departments. Relatives seemed to believe that mental hospitals are not appropriate places in which to treat their loved ones, even though most of them felt that they were alone in coping with the burden of their ill relative's disease. Most of the relatives agreed that people who have schizophrenia should be allowed to vote, but they appeared to have a stricter attitude toward affective rights, such as the patient's right to get married and have children, and tended to perceive their loved ones as being subject to social discrimination. The findings of this study may be useful for developing psychoeducational intervention and sensitization campaigns for the general population.

Adult↗