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T Rubino

Publications and source records attributed to T Rubino.

At least 37 records · Page 2Linked to original sources
PubMed1996

[The phantom breast syndrome].

BACKGROUND: The phantom breast syndrome (PBS) is a complication of mastectomy which consists of a sensation of breast persistence after mastectomy. MATERIALS, PATIENTS AND METHODS: The incidence, clinical course and location of PBS in 97 operated women were studied for a 15-year period. All women were interviewed in postoperative follow-up controls after mastectomy. RESULTS: The incidence of PBS was 29 patients out of the 97 total. The syndrome was present for more than 48 months in eleven of these patients. In most cases the location of "phantom sensations" was the nipple (15 cases) and the entire breast in five patients. In only three patients was phantom breast pain (PBP) reported whereas some discomfort was reported by the other patients. CONCLUSIONS: The incidence of PBS in our series was similar to that reported by other authors, but PBP was less common. Neither postoperative sequelae nor the antitumoral specific therapy seemed to have influence on the emergence of PBS.

Adult↗
PubMed1995

Morphine withdrawal syndrome and G protein expression: a study of the time course in the rat central nervous system.

We followed the changes in G protein alpha subunit expression and levels throughout the brain during the naltrexone-precipitated withdrawal syndrome in morphine-dependent rats. Intraperitoneally injected naltrexone (10 mg/kg) in rats made tolerant to morphine resulted in sustained withdrawal. Additional naltrexone doses 6, 24 and 72 h later still induced a significant abstinence syndrome. At the fifth naltrexone injection (8 days later) counted signs were completely resolved but checked ones were not. Besides the behavioural modifications, opiate withdrawal affected G protein expression in the central nervous system. In situ hybridization showed that G alpha s and G alpha o mRNA, whose levels are increased in tolerance, changed further during opiate withdrawal. Specifically, as alpha s mRNA in the hypothalamus was reduced after the first naltrexone injection and reached the control level with subsequent doses. However, alpha a mRNA expression in the olfactory system remained elevated after repeated naltrexone injections, declining to the control value of only after the fifth dose. The amounts of G alpha s and G alpha o protein closely followed the time course of mRNA. The relationship between behavioural and biochemical parameters is discussed, together with the regional selectivity of the modifications.

Animals↗
PubMed1994

Chronic CP-55,940 alters cannabinoid receptor mRNA in the rat brain: an in situ hybridization study.

Using in situ hybridization we found that chronic treatment with CP-55,940 (0.4 mg kg-1, i.p. daily for 11 days), a synthetic cannabinoid receptor ligand, changed cannabinoid receptor mRNA levels in rat brain. CP-55,940 produced the expected tolerance: the decrease in locomotor activity (75%) caused by an acute dose was diminished to 25% after the 11 days of treatment. Thirty minutes after the last injection the animals were killed and in situ hybridization indicated that the levels of cannabinoid receptor mRNA in the caudate-putamen were reduced by 33%, with no alteration in the other brain areas. We suggest that the altered cannabinoid receptor expression is part of the adaptive changes underlying cannabinoid tolerance.

Animals↗
PubMed1994

Intestinal effect of morphine 6-glucuronide: in vivo and in vitro characterization.

Morphine 6-glucuronide, a major metabolite of morphine with potent analgesic actions, is a potent inhibitor of intestinal motility when administered to rats by the intracerebroventricular (i.c.v.) route. Morphine 6-glucuronide was 62-fold more active than morphine in inhibiting gastrointestinal transit, whereas it was only 25-fold more potent in abolishing intestinal migrating myoelectric complexes. Pretreatment with naloxone (5 micrograms/rat i.c.v.) completely prevented the disappearance of migrating myoelectric complexes induced by the morphine metabolite. In contrast, in the guinea pig ileum bioassay, morphine 6-glucuronide and morphine inhibited the electrically evoked contractions of the tissue with similar potency, although in the guinea pig ileum binding assay the metabolite showed 4-fold lower affinity for the opiate receptor. The low naloxone Ke values against morphine 6-glucuronide or morphine indicated that the action of both drugs in guinea pig ileum was mediated by mu-opioid receptors.

Animals↗
PubMed1994

Effect of chronic exposure to naltrexone and opioid selective agonists on G protein mRNA levels in the rat nervous system.

The in situ hybridization technique was used to investigate the effect on G protein alpha subunit expression throughout the brain of rats chronically infused with naltrexone (70 micrograms/microliters, 1 microliter/h), DAGO (0.5 micrograms/microliter, 1 microliter/h), DADLE (11.4 micrograms/microliters, 1 microliter/h), DPDPE (3.4 micrograms/microliters, 1 microliter/h) and U-50,488H (4 micrograms/microliters, 1 microliter/h). Prolonged exposure to naltrexone did not modify G protein alpha subunit mRNA expression, whereas DADLE and U-50,488H, respectively, increased the levels of alpha s and alpha o mRNA in specific brain regions. In particular, a 15% increase in alpha s expression was only observed in the dorsomedial hypothalamic nucleus of rats undergoing chronic DADLE infusion: a 15% increase in alpha o levels was detected in the claustrum and endopiriform nucleus of rats chronically treated with U-50,488H. These are the first in vivo data to demonstrate that only chronic stimulation with an opioid agonist (morphine and/or DADLE and U-50,488H) is capable of modifying G protein alpha subunit mRNA. The regional selectivity of these modifications is discussed, together with the receptor specificity of the opioid effects.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1993

Cholera toxin antagonizes morphine-induced catalepsy through a cyclic AMP-independent mechanism.

We studied the effect of intracerebroventricular pretreatment with pertussis toxin and cholera toxin on morphine catalepsy in rats. Pertussis toxin (1 micrograms/rat, two, three and six days before) did not affect catalepsy evoked by central morphine. Cholera toxin (1 micrograms/rat) did not affect morphine catalepsy after 24 h and 48 h, but significantly reduced it (about 60%) after three and five days. Ten days later the morphine response had totally recovered. This effect was selective, since morphine analgesia was not modified. The reduction of catalepsy appeared unrelated to the ability of cholera toxin to raise cAMP levels, as demonstrated by the different time course of changes in striatal cholera toxin-stimulated adenylate cyclase activity. The effect required an intact cholera toxin molecule and did not occur with a similar dose of cholera toxin-B subunit. These findings demonstrate that catalepsy is an opioid effect not linked to pertussis toxin-sensitive G proteins and suggest that the Gs protein might be involved.

Adenylate Cyclase Toxin↗
PubMed1993

In situ hybridization reveals specific increases in G alpha s and G alpha o mRNA in discrete brain regions of morphine-tolerant rats.

In situ hybridization histochemistry has been used to detect the basal distribution of mRNA encoding the alpha subunit of Gs, Go and Gi2 proteins throughout the rat brain. Based on these data we investigated the effect of chronic morphine on the content of these G protein alpha subunits mRNA. We observed an increase in the expression of alpha s and alpha o messages of chronically morphine-treated animals, while no changes were seen in alpha i2 mRNA. Specifically a 30% increase in expression for alpha s was seen only in the paraventricular nucleus of hypothalamus and a 20% elevation for alpha o was detected in the claustrum and endopiriform nucleus. Immunoblotting analysis was used to correlate the changes in alpha s and alpha o messages with equivalent changes in protein levels. Chronic morphine significantly increased alpha s amounts in the hypothalamus (70%), and produced a minor elevation (30%) in G alpha o levels in the olfactory area. Our results indicate that in discrete brain regions altered G protein expression is part of the adaptive changes underlying opiate tolerance.

Animals↗
PubMed1992

Influence of omega-conotoxin on morphine analgesia and withdrawal syndrome in rats.

The effect of omega-conotoxin on opiate analgesia and withdrawal syndrome was investigated in rats. omega-Conotoxin given i.c.v. and i.p. caused weak analgesia in the tail-flick test. When the toxin (20 ng/rat) was given i.c.v. immediately before morphine (1.5 micrograms/rat i.c.v.) the resultant analgesic effect was additive. In contrast, the analgesia elicited by morphine (3 micrograms/rat i.c.v.) was greatly reduced after 24-h pretreatment with the toxin (20 ng/rat i.c.v.). The systemic administration of the toxin (10 micrograms/kg i.p.) did not affect morphine analgesia whether omega-conotoxin was coadministered with morphine (2.5 mg/kg i.p.) or was given 24 h before the opiate (5 mg/kg i.p.). omega-Conotoxin i.c.v. injected in morphine-dependent rats 15 min before naloxone challenge significantly attenuated the abstinence syndrome. On the contrary systemic administration of omega-conotoxin failed to suppress the morphine withdrawal syndrome. The present results suggest that omega-conotoxin affects both acute and chronic effects of morphine.

Analgesia↗
PubMed1992

Further investigations on the antipropulsive effect of centrally administered histamine and its relation with morphine.

The effect of intracerebroventricularly (i.c.v.) administered histamine (100 micrograms/rat) on intestinal myoelectrical activity was investigated in the jejunum of fasted rats. Histamine caused the disappearance of phase III and a partial reduction of phase II of migrating myoelectric complexes. This effect was antagonized by i.c.v. pretreatment with mepyramine (10 micrograms/rat), an H1 receptor antagonist. Lesions of central noradrenergic neurons by i.c.v. injection of the neurotoxin 6-hydroxydopamine strongly reduced both the inhibition of intestinal propulsion and the migrating myoelectric complexes profile induced by i.c.v. histamine, whereas pretreatment with p-chlorophenylalanine, a selective depletor of serotonin stores, had no effect. It thus appears that aminergic pathways are involved in the visceral effects of central histamine. Mepyramine (200 micrograms/rat i.c.v.) partially reduced the slowing of intestinal transit induced by high doses of morphine. Pretreatment with compound 48/80 (10 micrograms/rat i.c.v.), a mast cell degranulator, but not with alpha-fluoromethylhistidine, an irreversible inhibitor of histidine decarboxylase, reduced the antipropulsive action of i.c.v. morphine to the same extent as mepyramine, suggesting that histamine released from cerebral mast cells by high doses of morphine could contribute to the intestinal inhibition by morphine.

Animals↗
PubMed1991

Pertussis toxin pretreatment affects opiate/nonopiate and stress-induced analgesia differently.

Intracerebroventricular injection of pertussis toxin (PTX, 1 microgram/rat) six days before the hot plate test abolished analgesia induced by central morphine. The toxin did not affect analgesia evoked by central neurotensin or ASU 1-7 eel calcitonin. PTX pretreatment also attenuated footshock-induced analgesia (FSIA) delivered to all four paws. When the shock was restricted to the front paws, PTX consistently lowered postshock tail flick latencies, but did not reduce analgesia resulting from shock delivered to the hind paws. It thus appears that PTX-sensitive G-proteins are an essential transduction step needed to initiate the molecular events underlying opiate analgesia evoked by either morphine or shock. In contrast, the signal transduction mechanism subsequent to the stimulation of neurotensin or calcitonin receptors, and to the nonopiate FSIA, appears not to involve PTX-sensitive G-proteins.

Animals↗
PubMed1991

Bombesin receptor antagonists. 2. Analogues based on substance P antagonists.

Although bombesin (BN) and substance P share only the C-terminal dipeptide amide, some substance P receptor antagonists are also weak bombesin receptor antagonists. In order to increase the selectivity of the antagonism for the BN receptor, a series of hybrid peptides were synthesized by the solid-phase methodology, and screened on 3T3 fibroblasts for binding and mitogenic activity. The analogues inhibiting BN-induced thymidine incorporation were further tested for peripheral (amylase release and urinary bladder contraction) and central activity (grooming behaviour).

3T3 Cells↗
PubMed1990

Pertussis toxin modifies the effect of central morphine on rat intestinal motility.

To find whether the antipropulsive effect of morphine administered intracerebroventricularly (i.c.v.) depends on a G-protein-mediated mechanism, we studied the effect of i.c.v. pertussis toxin (PTX) pretreatment on morphine-induced inhibition of intestinal motility. The influence of PTX was evaluated on intestinal transit (charcoal meal test) and by monitoring of intestinal myoelectrical activity. The antitransit effect of morphine (10 micrograms/rat) was antagonized by about 70% 3, 6, 9 and 12 days after PTX pretreatment (1 microgram/rat) and it was partially restored after 25 days. I.c.v. morphine abolished the regular appearance of the myoelectric migrating complex (MMC) recorded in the rat jejunum and this effect was completely antagonized by PTX pretreatment. When morphine was injected 25 days after PTX, it significantly reduced MMC frequency, confirming the partial recovery seen in the transit experiments. The pertussis toxin-catalyzed ADP ribosylation of a 39-41 kDa substrate in membranes prepared from hypothalamus and midbrain of rats injected with toxin 6 days before was strongly reduced as compared to the controls. On the contrary, after 25 days, ADP ribosylation was the same in treated and control rats. Thus the antipropulsive effect of central morphine could be initiated at receptor sites which interact with G-protein substrates of pertussis toxin.

Adenosine Diphosphate↗
PubMedDate not supplied

Perinatal delta9-tetrahydrocannabinol exposure did not alter dopamine transporter and tyrosine hydroxylase mRNA levels in midbrain dopaminergic neurons of adult male and female rats.

We have recently demonstrated that the magnitude of L-3,4-dihydroxyphenylacetic acid (DOPAC) lowering effect caused by amphetamine in midbrain dopaminergic neurons of adult rats was lesser in animals that had been perinatally exposed to delta9-tetrahydrocannabinol (delta9-THC) than controls. In the present study, we have examined whether this loss in the responsiveness to amphetamine might be due to changes at the level of dopamine transporter (DAT), the main molecular site for the action of amphetamine, following the perinatal exposure to delta9-THC. To this end, we have analyzed DAT mRNA levels, by using in situ hybridization, in the substantia nigra and ventral tegmental area, the areas where cell bodies of DAT-containing midbrain neurons are located, of adult male and female rats that had been perinatally exposed to delta9-THC. In addition, we also analyzed mRNA levels of tyrosine hydroxylase (TH), the rate-limiting enzyme in DA synthesis. Results were as follows. Both adult male and female rats that had been perinatally exposed to delta9-THC exhibited similar mRNA levels to controls for both DAT and TH in the substantia nigra as well as in the ventral tegmental area. This observation makes it difficult to support the idea that the differences found in adulthood after pharmacological challenges were caused by irreversible changes at the level of gene expression for these two key proteins.

Animals↗
PubMedDate not supplied

Endocannabinoids in the immune system and cancer.

The present review focuses on the role of the endogenous cannabinoid system in the modulation of immune response and control of cancer cell proliferation. The involvement of cannabinoid receptors, endogenous ligands and enzymes for their biosynthesis and degradation, as well as of cannabinoid receptor-independent events is discussed. The picture arising from the recent literature appears very complex, indicating that the effects elicited by the stimulation of the endocannabinoid system are strictly dependent on the specific compounds and cell types considered. Both the endocannabinoid anandamide and its congener palmitoylethanolamide, exert a negative action in the onset of a variety of parameters of the immune response. However, 2-arachidonoylglycerol appears to be the true endogenous ligand for peripheral cannabinoid receptors, although its action as an immunomodulatory molecule requires further characterization. Modulation of the endocannabinoid system interferes with cancer cell proliferation either by inhibiting mitogenic autocrine/paracrine loops or by directly inducing apoptosis; however, the proapoptotic effect of anandamide is not shared by other endocannabinoids and suggests the involvement of non-cannabinoid receptors, namely the VR1 class of vanilloid receptors. In conclusion, further investigations are needed to elucidate the function of endocannabinoids as immunosuppressant and antiproliferative/cytotoxic agents. The experimental evidence reviewed in this article argues in favor of the therapeutic potential of these compounds in immune disorders and cancer.

Animals↗