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P Fadda

Publications and source records attributed to P Fadda.

At least 19 recordsLinked to original sources
PubMed2004

Thyroid involvement in patients with overt HCV-related mixed cryoglobulinaemia.

BACKGROUND: Mixed cryoglobulinaemia (MC), a systemic vasculitis associated with hepatitis C virus (HCV) infection in >90% of cases, is frequently complicated by multiple organ involvement. The prevalence of thyroid disorders in MC has not yet been studied. AIM: To investigate the prevalence and clinical features of thyroid involvement in patients with HCV-associated MC (HCV + MC). DESIGN: Case-control study. METHODS: HCV + MC patients (n = 93, 17 men and 76 women, mean +/- SD age 63 +/- 10 years, mean disease duration 14 +/- 7 years) consecutively referred to the Rheumatology Unit were matched by sex and age (+/- 2 years) to (i) 93 patients with chronic C hepatitis (CH) without MC and (ii) 93 healthy (HCV-negative) controls from the local population. Measurements included prevalence of hypo- or hyperthyroidism, thyroid autoantibodies, thyroid nodules and thyroid cancer. RESULTS: By McNemar's chi(2) test, the following thyroid abnormalities were significantly more frequent in HCV + MC patients than in HCV-negative controls: serum anti-thyroperoxidase autoantibody (AbTPO) (28% vs. 9%, p = 0.001); serum AbTPO and/or anti-thyroglobulin autoantibody (31% vs. 12%, p = 0.004); subclinical hypothyroidism (11% vs. 2%, p = 0.038); thyroid autoimmunity (35% vs. 16%, p = 0.006). Serum AbTPO were also significantly more frequent in HCV + MC patients than in CH controls (28% vs. 14%, p = 0.035). DISCUSSION: The prevalence of thyroid disorders is increased in patients with HCV-related mixed cryoglobulinaemia. We suggest careful monitoring of thyroid function in these patients.

Aged↗
PubMed2001

Kartagener's syndrome and rheumatoid arthritis: an unusual association.

We report the case of a 66-year-old caucasian woman affected by Kartagener's syndrome (KS), a genetically transmitted disorder characterised by situs viscerum inversus, bronchiectasis and sinusitis, who also developed rheumatoid arthritis (RA). The impaired mucociliary function typical of KS caused recurrent paranasal sinus and lung infections, as shown by CT scans of the sinuses and chest. The coexistence of KS and RA in our patient was probably accidental. Given the small number of patients in whom an association of the two disorders has been described, it is impossible to establish whether KS might play a role in the pathogenesis of RA.

Aged↗
PubMed2000

Synthesis, molecular modeling, and opioid receptor affinity of 9, 10-diazatricyclo[4.2.1.1(2,5)]decanes and 2,7-diazatricyclo[4.4.0. 0(3,8)]decanes structurally related to 3,8-diazabicyclo[3.2. 1]octanes.

Various lines of evidence, including molecular modeling studies, imply that the endoethylenic bridge of 3,8-diazabicyclo[3.2. 1]octanes (DBO, 1) plays an essential role in modulating affinity toward mu opioid receptors. This hypothesis, together with the remarkable analgesic properties observed for N(3) propionyl, N(8) arylpropenyl derivatives (2) and of the reverted isomers (3), has prompted us to insert an additional endoethylenic bridge on the piperazine moiety in order to identify derivatives with increased potency toward this receptor class. In the present report, we describe the synthesis of the novel compounds 9,10-diazatricyclo[4.2. 1.1(2,5)]decane (4) and 2,7-diazatricyclo[4.4.0.0(3,8)]decane (5), as well as the representative derivatives functionalized at the two nitrogen atoms by propionyl and arylpropenyl groups (6a-e, 7a-d). Opioid receptor binding assays revealed that, among the compounds tested, the N-propionyl-N-cinnamyl derivatives 6a and 7a exhibited the highest mu-receptor affinity, and remarkably, compound 7a displayed in vivo (mice) an analgesic potency 6-fold that of morphine.

Analgesics↗
PubMed1999

Differences in the opioid system in selected brain regions of alcohol-preferring and alcohol-nonpreferring rats.

BACKGROUND: Previous studies have suggested that alcohol-reinforcing effects are mediated by the endogenous opioid system, which, in turn, stimulates mesolimbic dopaminergic neurotransmission. In addition, evidence obtained in both humans and rats indicates that genetic factors may influence alcohol-drinking behavior. In the present study, we examined several components of the opioid system in selected brain regions of rats bred selectively for their innate alcohol preference (Sardinian preferring = sP) or alcohol aversion (Sardinian nonpreferring = sNP). METHODS: To evaluate whether differences observed were consequent to alcohol intake, sP rats were divided into two subgroups, ethanol-naive sP (sP) and ethanol-experienced sP (sPexp). Opioid receptors were labeled, using [3H]naloxone (mu, delta, and kappa receptors), [D-Ala2,N-Me-Phe4,Gly,ol5]enkephalin ([3H]DAMGO; mu receptors), and [D-Ala2,D-Leu5]enkephalin ([3H]DADLE; delta receptors), by means of quantitative autoradiography. Enkephalin and dynorphin mRNA contents were measured by in situ hybridization by using 25- and 47-base oligonucleotide probes with sequences complementary to mRNA encoding rat enkephalin or dynorphin. RESULTS: Our results revealed a significant reduction of opioid receptors in caudate-putamen nucleus and in the shell portion of the nucleus accumbens in sP compared with sNP rats. Alcohol intake partially reversed this reduction in the caudate-putamen nucleus. In addition, enkephalin mRNA expression was found to be decreased in the ventral part of caudate-putamen nucleus and increased in the cerebral cortex of sP rats compared with sNP rats; no significant differences were found in dynorphin mRNA expression in any of the brain areas examined. CONCLUSIONS AND SIGNIFICANCE: Differences observed between the two lines of rats may implicate that genetic modifications in the opioid system are possibly responsible for the innate preference of sP rats toward alcohol intake. At the same time, it cannot be excluded that other functions might also be affected to some degree.

Alcoholism↗
PubMed1997

Stress-induced sleep deprivation modifies corticotropin releasing factor (CRF) levels and CRF binding in rat brain and pituitary.

Electroencephalographic (EEG) studies have shown that corticotropin-releasing factor (CRF) administration induces EEG activation, decreases sleep time both in rats and humans and modifies the sleep pattern in sleep deprived rats. In the present study we have investigated whether CRF neuronal activity could be altered in a situation of disrupted sleep-wake cycle. Sleep deprivation (SD) was induced by keeping the rat for 72 h on a small platform (7 cm) surrounded by water. Immediately after the SD period rats were killed and CRF levels and CRF receptor binding were evaluated in different brain areas. A marked increase in CRF levels was present in the striatum (+224%), limbic areas (+144%) and pituitary (+42%) whereas the hypothalamic CRF content was reduced (-57%). A significant decrease in CRF binding was found in the striatum (-33%) and pituitary (-38%) of sleep deprived rats. These results indicate that CRF neuronal activity is stimulated by SD, suggesting that CRF might play an important role in the physiological regulation of the sleep-wake cycle and that an altered CRF neuronal activity might be involved in behavioral modifications related to sleep disturbances.

Animals↗
PubMed1997

Antinociceptive action of DBO 17 and DBO 11 in mice: two 3,8 diazabicyclo (3.2.1.) octane derivates with selective mu opioid receptor affinity.

Two 3,8 diazabicyclo (3.2.1.) octane derivates, namely DBO 17 and DBO 11, were studied for the opioid-like activity. In the rat brain membrane preparation binding studies, DBO 17 and DBO 11 showed a high affinity and selectivity for the mu opioid receptor (Ki's: 5.1 and 25 nM, respectively). DBO 17 and DBO 11 inhibited the nociceptive response in the hot-plate test of mice with ED50 values of 0.16 mg/kg and 0.44 mg/kg, respectively. The antinociceptive action of both DBO 17 and DBO 11 was blocked by naloxone. Tolerance to the antinociceptive action of DBO 17 and DBO 11 was present after 13 and 7 days of repeated treatment, respectively. Both DBO 17 and DBO 11 were ineffective in morphine-tolerant mice and vice versa. Chronic treatments (three times daily for seven consecutive days) of DBO 17 and DBO 11 induced a naloxone-precipitated withdrawal syndrome in DBO 17 treated mice similar to that in morphine treated mice, whereas in DBO 11 treated mice abstinence signs were virtually absent. These results indicate an interesting pharmacological profile that suggests these compounds as possible new candidates for the clinical treatment of pain.

Analgesia↗
PubMed1997

Chronic morphine and naltrexone fail to modify mu-opioid receptor mRNA levels in the rat brain.

Previous radioligand-binding studies have reported conflicting results concerning the effect of chronic morphine administration on the regulation of mu-opioid receptor (MOR) density. On the other hand, chronic administration of an opioid antagonist, such as naltrexone, has been shown to increase the density of the MOR. In order to determine if the changes in the MOR are associated with alterations in receptor mRNA levels, we investigated MOR gene expression following chronic treatment with morphine and/or naltrexone. MOR mRNA levels, determined by the ribonuclease protection assay (RPA), were unchanged with respect to control during chronic morphine treatment and morphine withdrawal in each of the analysed brain areas. Furthermore, chronic administration of naltrexone did not result in changes of MOR mRNA levels in rat striatum of naive and morphine-dependent rats, suggesting that the up-regulation of the MOR density, at least in this tissue, is not regulated at transcriptional level.

Animals↗
PubMed1996

C-Fos expression as a molecular marker in corticotropin-releasing factor-induced seizures.

Expression of Fos-like protein has been shown to increase after seizures in several types of experimentally induced epilepsies. The intracerebroventricular (icv) injection of murine corticotropin-releasing factor (CRF) in rats (10 micrograms), shows an electroencephalographic (EEG) spiking activity restricted to the amygdaloid-hippocampal area. This EEG seizure pattern represents a unique model of localized epileptic activity induced by a neuropeptide. C-fos expression after icv CRF has been considered a useful tool in mapping areas involved in stress and in seizure activity. Our results show that 1 microgram and 10 micrograms CRF are able to induce c-fos activation in several brain areas. Moreover, the present study not only details c-fos expression increase in brain areas directly involved in spiking activation, such as the amygdaloid-hippocampal region, but also maps the possible contribution of other regions to seizure manifestations.

Animals↗
PubMed1995

Chronic imipramine, L-sulpiride and mianserin decrease corticotropin releasing factor levels in the rat brain.

Among clinically effective antidepressant drugs, the action mechanism of mianserin has recently been related to variations in corticotropin releasing factor (CRF) levels in the rat locus coeruleus. We describe a specific effect on CRF levels after chronic treatment with different antidepressants: mianserin (10 mg/kg), imipramine (20 mg/kg), both for 21 days, or L-sulpiride (1 mg/kg) for 15 days. While all antidepressants used greatly decreased CRF concentrations in the hypothalamus, only mianserin decreased CRF concentrations by 40% in extrahypothalamic sites. Acute treatments failed to modify CRF levels. Chronic treatment with mianserin did not affect CRF density either in the hypothalamus or the extrahypothalamic areas. This new finding may add another facet to the therapeutic action of certain antidepressants and in particular to the atypical profile of mianserin.

Animals↗
PubMed1995

Sleep deprivation in the rat: an animal model of mania.

The model of sleep deprivation in rats by the platform method has been extensively studied in our laboratory as a possible animal model of mania. At the end of the period of sleep deprivation, the rat does not fall asleep as soon as it is returned to its home cage, but shows a period of wakefulness of about 30 min, during which the animal presents a cohort of symptoms that appear to mimic those present in idiopathic mania. In particular, during this period the animal displays insomnia, a high degree of hyperactivity, irritability, aggressiveness, hypersexuality and stereotypy. Haloperidol (0.2 mg/kg) was effective in reducing latency to sleep, while L-sulpiride was much weaker (< 50 mg/kg). The dopamine D1 receptor antagonist SCH 23390 exhibited an extremely high potency and efficacy in reducing sleep latency, a significant effect being observed with 3 micrograms/kg. The administration of the specific D1 receptor agonist SKF 38393 markedly prolonged the period of insomnia with the correlated behavioral syndrome. When lithium was added to the diet and consumed during the sleep deprivation period in adequate amounts to produce serum lithium levels of 0.7-1.0 mEq/l, sleep latency and locomotor activity were significantly reduced. The administration of naloxone (1-10 mg/kg) reduced the latency to sleep in a dose-related manner. By contrast, morphine (1 and 5 mg/kg, i.p.), beta-endorphin and [D-Ala2,D-Leu5]enkephalin (i.c.v., 2 and 1 micrograms, respectively) markedly prolonged the insomnia. The model not only represents a confirmation in the rat that sleep loss often precedes and may trigger a manic episode in man, but suggests that an opioid-dopamine interaction may play a pathogenetic role in mania.

Animals↗
PubMed1993

Dopamine and opioids interactions in sleep deprivation.

1. Sleep deprivation induced by the platform technique is considered to be a heavy stressful situation in rats. At the end of the sleep deprivation period (72 hrs) the rat displayed particular behavior characterized by wakefulness, a high degree of motor and exploratory activity, increased alertness and reactivity to environmental stimuli. 2. Our results indicate that this behavior is potently antagonized by the administration of D1 antagonist SCH 23390 and by the opioid antagonist naloxone. 3. We also show that concomitantly to this behavior, an increased number of D1 receptors associated with an increased dopamine-stimulated adenylate cyclase activity is present in the limbic system but not in the striatum of these animals. On the contrary, a decreased Bmax of mu and delta opioid receptors was found in the same brain areas. 4. These data suggest an active role of limbic dopamine and opioid system in the generation of arousal and insomnia related to sleep deprivation-induced stress.

Adenylyl Cyclases↗
PubMed1993

Synthesis and opioid receptor affinity of bivalent ligands derived from 3,8-diazabicyclo(3.2.1)octanes.

A new series of bivalent ligands (2a-d), derived from the previously reported analgesic 3-cinnamyl-8-propionyl-3,8-diazabicyclo(3.2.1)octane (1a), has been synthesized and tested in vitro for their affinity towards opioid receptors and in vivo for their analgesic potency. None of the new compounds showed either appreciable affinity for opioid receptors or analgesic activity comparable to that of the model 1a.

Analgesics↗
PubMed1992

Dopamine D1 and opioid receptor binding changes in the limbic system of sleep deprived rats.

Sleep deprivation induced by the platform technique is considered to be a heavy stressful situation in rats. At the end of the sleep deprivation period (72 h) the rat displayed particular behavior characterized by wakefulness, a high degree of motor and exploratory activity, increased alertness and reactivity to environmental stimuli. Our previous results indicated that this behavior was potently antagonized by the administration of the D1 selective antagonist SCH 23390 and by the opioid antagonist naloxone. In this paper we show that concomitantly to this behavior, an increased number of D1 receptors associated with an increased dopamine-stimulated adenylate cyclase activity is present in the limbic system but not in the striatum of these animals. On the contrary, a decreased Bmax of mu and delta opioid receptors was found in the same brain area. These data suggest an active role of limbic dopamine and opioid systems in the generation of arousal and insomnia related to sleep deprivation-induced stress.

Animals↗
PubMed1991

Sleep deprivation decreases mu and delta opioid receptor binding in the rat limbic system.

Sleep deprivation induced by the platform technique is considered to be a heavy stressful situation in rats. At the end of the sleep deprivation period (72 h) the rat displayed particular behavior characterized by wakefulness, a high degree of motor and exploratory activity, increased alertness and reactivity to environmental stimuli. Our previous results indicated that this behavior was antagonized by the administration of the opioid receptor antagonist naloxone and increased by opioid agonists. In this paper we show that concomitantly with this behavior, a decreased Bmax of mu and delta opioid receptors is present in the limbic system of these animals. These data suggest an active role of limbic mu and delta receptors in the generation of arousal and insomnia related to sleep deprivation induced stress.

Animals↗
PubMed1990

Sleep deprivation increases dopamine D1 receptor antagonist [3H]SCH 23390 binding and dopamine-stimulated adenylate cyclase in the rat limbic system.

Sleep deprivation induced by the platform technique is considered to be a heavy stressful situation in rats. At the end of the sleep deprivation period (72 h) the rats displayed particular behaviour characterized by wakefulness, a high degree of motor and exploratory activity, increased alertness and reactivity to environmental stimuli. Our previous results indicated that this behaviour was potently antagonized by the administration of the D1-selective antagonist SCH 23390. In this paper we show that concomitantly to this behaviour, an increased number of D1 receptors associated with an increased dopamine-stimulated adenylate cyclase activity is present in the limbic system but not in the striatum of these animals. These data suggest an active role of limbic D1 receptors in the generation of arousal and insomnia related to sleep deprivation induced stress.

Adenylyl Cyclases↗