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T Palomo

Publications and source records attributed to T Palomo.

At least 37 records · Page 2Linked to original sources

Effects of MAO inhibitors upon MPTP mice chronically treated with suprathreshold doses of L-dopa.

Groups of mice were administered either saline or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (2 X 40 mg / kg, s.c., separated by a 24-hour interval) 4-6 weeks prior to behavioural testing. At testing, all the MPTP-injected mice were repeatedly administered L-dopa (20 mg / kg, s.c., five times each week, Monday-Friday), by applying a procedure that induced a severe reduction of motor activity parameters from Day 1 to Day 25. Control (uninjected mice) received only saline and were retained only for neurochemical analysis. In each of three experiments, following the reduction of the activity-stimulating effects of L-dopa by repeated administration, a restorative effect of different monoamine oxidase (MAO) inhibitors was tested by co-administration of the test compounds (irreversible MAO-B inhibitor, reversible MAO-A inhibitors, or irreversible MAO-A / mixed MAO inhibitors) with L-dopa (20 mg / kg). In each case the MAO inhibitor was injected 60 min prior to L-dopa. L-Deprenyl (3 or 10 mg / kg, s.c.), in combination with L-dopa, reinstated locomotion and total activity, but not rearing, dose-dependently, in L-dopa-tolerant mice. The reversible MAO-A inhibitors, amiflamine and alpha-ethyltryptamine, in combination with L-dopa, reinstated locomotion and total activity, leaving rearing unaffected; Ro 41-1049 (3 mg / kg, s.c.) restored all three parameters of activity; locomotor activity was restored by all three doses (1, 3, and 10 mg / kg, s.c.). On the other hand, neither the irreversible MAO-A inhibitor, clorgyline, nor the mixed MAO inhibitor, phenelzine, produced any directly effective restorative increments. Neurochemical analysis confirmed the severe striatal dopamine depletion of MPTP-treated mice. These results demonstrate a synergistic and restorative action of combining certain MAO inhibitors, namely the reversible MAO-A inhibitors, with the suprathreshold dose of L-dopa in MPTP-treated, L-dopa-tolerant mice.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Chronic (-)-delta9-tetrahydrocannabinol treatment induces sensitization to the psychomotor effects of amphetamine in rats.

Clinical and basic research studies have linked cannabinoid consumption to the onset of psychosis, specially schizophrenia. In the present study we have evaluated the effects of the natural psychoactive constituent of Cannabis (-)-delta9-tetrahydrocannabinol on the acute actions of the psychostimulant, D-amphetamine, on behaviour displayed by male rats on a hole-board, a proposed animal model of amphetamine-induced psychosis. Cannabinoid-amphetamine interactions were studied (1) 30 min after acute injection of (-)-delta9-tetrahydrocannabinol (0.1 or 6.4 mg/kg, i.p.); (2) 30 min after the last injection of 14-daily treatment with (-)-delta9-tetrahydrocannabinol (0.1 or 6.4 mg/kg) and 3) 24 h after the last injection of 14-daily treatment with (-)-delta9-tetrahydrocannabinol (6.4 mg/kg). Acute cannabinoid exposure antagonized the amphetamine-induced dose-dependent increase in locomotion, exploration and the decrease in inactivity. Chronic treatment with (-)-delta9-tetrahydrocannabinol resulted in tolerance to this antagonistic effect on locomotion and inactivity but not on exploration, and potentiated amphetamine-induced stereotypies. Lastly, 24 h of withdrawal after 14 days of cannabinoid treatment resulted in sensitization to the effects of D-amphetamine on locomotion, exploration and stereotypies. Since (-)-delta9-tetrahydrocannabinol is a cannabinoid CB1 receptor agonist, densely present in limbic and basal ganglia circuits, and since amphetamine enhances monoaminergic inputs (i.e., dopamine, serotonin) in these brain areas, the present data support the hypothesis of a role for the cannabinoid CB1 receptor as a regulatory mechanism of monoaminergic neuron-mediated psychomotor activation. These findings may be relevant for the understanding of both cannabinoid-monoamines interactions and Cannabis-associated psychosis.

Amphetamine↗

Tolerance to a suprathreshold dose of L-Dopa in MPTP mice: effects of glutamate antagonists.

Three experiments were performed to study the development and manipulation of tolerance to a suprathreshold dose of L-Dopa (20 mg/kg, s.c.) in MPTP-treated and control (saline-injected) C57 Bl/6 mice. The motor activity reinstatement effect of this dose of L-Dopa upon MPTP-treated mouse behaviour deteriorated from the 13th injection (Test Day 8) of L-Dopa onwards and reached basal level (i.e. no stimulatory effects of the drug) by the 16th administration (Test Day 10). Administration of L-Dopa to control mice reduced locomotor and rearing activity throughout the tolerance development period (Test Days 1-12) during the first hour after injection, and then increased locomotor activity during the second hour. The effects of combining either a noncompetitive, MK-801, or a competitive, CGP 40116, glutamate antagonist with L-Dopa, following tolerance development, were assessed in MPTP mice on the 23rd day of L-Dopa administration (Test Day 13). MK-801 (0.1 mg/kg, s.c.) reinstated the locomotory and rearing behaviour induced by L-Dopa; CGP 40116 did so also to a greater extent in the dose range 0.01 to 0.03 mg/kg. These results indicate that MPTP-treated mice continue to offer a useful parkinsonian model also for the examination of different aspects of the "wearing-off" phenomenon of L-Dopa tolerance and in particular the putative glutamatergic involvement. The clinical consequences may be far-reaching for the utility of L-Dopa in Parkinson's disease, whether the effects demonstrated be of a reinstatement or synergistic nature, once therapeutically adequate glutamate antagonists are more readily available.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Effects of co-administration of anticonvulsant and putative anticonvulsive agents and sub/suprathreshold doses of L-dopa upon motor behaviour of MPTP-treated mice.

The effects of co-administration of the dopamine precursor, L-Dopa, with anticonvulsant and putative anticonvulsive agents upon the motor activity of hypoactive MPTP-treated C57 BL/6 mice were measured in six experiments. In each case, MPTP (2 x 40 mg/kg, s.c., separated by a 24-hr interval) was administered four to six weeks prior to behavioural testing. Thus, the effects of these agents combined with either a single acute, subthreshold dose (5 mg/kg, s.c.) of L-Dopa, or, with chronically-administered, suprathreshold doses (20 mg/kg, s.c.) of L-Dopa were studied. In the former, lamotrigine, FCE 26743 and L-Deprenyl, injected 60 min before subthreshold L-Dopa (5 mg/kg), each induced an antiparkinsonian action in MPTP-treated mice that consisted of dose-specific, as opposed to dose-related, elevations of locomotion and rearing behaviour. In the latter, lamotrigine (all three measures of activity at 3 mg/kg), FCE 26743 (locomotion and total activity at 3; rearing at 1 and 3 mg/kg) and L-Deprenyl (locomotion and total activity at 1 and 3mg/kg), but not phenytoin (neither at 1 nor 3 mg/kg), reinstated the motor activity-stimulating effects of the threshold dose of L-Dopa (20 mg/kg) in L-Dopa-tolerant, MPTP-treated mice. Neurochemical analyses confirmed severe DA depletions in MPTP-treated mice. Since neither lamotrigine, FCE 26743 nor L-Deprenyl, nor subthreshold L-Dopa, by themselves increased the motor behaviour of MPTP-treated mice, a synergistic effect of the co-administration is concluded. Further, since the suprathreshold dose of L-Dopa by itself failed to stimulate motor activity in the MPTP mice following chronic (25 daily injections) administrations of the compound, it is suggested that a restorative effect, in combination with lamotrigine, FCE 26743 or L-Deprenyl was evidenced. The potential therapeutic benefits of anticonvulsant or putative anticonvulsive compounds for parkinsonian symptoms are discussed.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Downregulation of rat brain cannabinoid binding sites after chronic delta 9-tetrahydrocannabinol treatment.

Specific cannabinoid receptors have been recently described in extrapyramidal and limbic areas and presumably might mediate the effects of marijuana exposure on behavioral processes related to those areas. In this work, we examined whether cannabinoid receptors exhibit downregulation as a consequence of the chronic exposure to delta 9-tetrahydrocannabinol (THC), which might explain certain tolerance phenomena observed in relation to motor and limbic effects of marijuana. To this end, we first characterized the binding of cannabinoid receptors, by using [3H]CP-55,940 binding assays, in the striatum, limbic forebrain, and ventral mesencephalon of male rats, and, second, we measured the density and affinity of those receptors in these brain areas after 7 days of a daily treatment with THC. Development of a tolerance phenomenon was behaviorally tested by using an open-field technique. Results were as follows. The three areas studies presented specific and saturable binding for the cannabinoid ligand, as revealed by their corresponding association and dissociation curves, displacement by THC, saturation curves, and Scatchard plots. A chronic treatment with THC produced the expected tolerance phenomenon: The decrease caused by an acute dose in spontaneous locomotor (49.4%) and exploratory (59.7%) activities and, mainly, the increase in the time spent by the rat in inactivity (181.7%) were diminished after 7 days of daily treatment (39.4, 40.4, and 31.7%, respectively). This tolerance was accompanied by significant decreases in the density of cannabinoid receptors in the striatum and limbic forebrain, the areas where nerve terminals for nigrostriatal and mesolimbic dopaminergic systems, respectively, which play an important role in those processes, are located.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

SUNCT syndrome: repetitive and overlapping attacks.

A 79-year-old patient had been suffering from right orbital pain attacks since he was 77. The pain, of an "electrical" or burning character, was moderate to severe in intensity. Single attacks lasted for 30-60 seconds each and were accompanied by prominent ipsilateral conjunctival injection and tearing as well as slight rhinorrhoea. The temporal pattern of attacks was irregular with spontaneous remissions alternating with unpredictable symptomatic phases. During active periods, attacks could be triggered by several precipitants acting on trigeminal and extra-trigeminal innervated areas. On most occasions, the patient had 2-3 attacks daily but, at worst, he might have almost continuous short-lasting attacks in periods of 1 to 3 hours length. When attacks had such frequency they presented either as repetitive or overlapping single episodes. According to the clinical features it is concluded that the case reported is a new case of SUNCT syndrome.

Aged↗

Pulmonary perivascular and interstitial inflammation in MRL/MpJ-lpr/lpr mice. III. Modulation by cyclophosphamide and sex hormones in 4- and 6-month-old animals.

Estradiol (E) abolished clearing of pulmonary inflammation in 2-month-old male MRL/MpJ-lpr/lpr (MRL/l) mice treated with cyclophosphamide (CY). To determine if this effect persisted in animals with advanced disease, we studied male and female MRL/l mice, aged 4 and 6 months (4M, 6M, 4F, and 6F, respectively). Mice were treated, beginning at 1 month of age, with saline, CY (12 mg/kg/day), CY + castration, CY + castration + testosterone (T) in females, and CY + castration + E in males. CY had no effect on pulmonary inflammation in 4M, possibly because of the development of relatively mild lesions. However, CY was highly effective in 6M. CY + castration + T significantly reduced overall inflammation in 6F and showed a trend in 4F. CY alone had a variable effect on bronchoalveolar lavage fluid (BALF) cells and BALF IgG in both males and females. However, concurrent treatment with T was required for histologic changes of pulmonary inflammation to fully respond to a high dose of CY in female mice. E-treated males had reduced responsiveness to CY.

Aging↗

Hemicrania continua. The first Spanish case: a case report.

The case of a patient suffering from strictly unilateral continuous headache, absolutely responsive to indomethacin is reported. This is the first Hemicrania continua case to be documented in Spain. The tyramine test resulted in anisocoria with the smaller pupil on the symptomatic side. A second tyramine test after one week on 75 mg indomethacin per day failed to produce anisocoria. Treatment was reduced to 25 mg indomethacin per day, and this dose was sufficient to control the headache completely.

Adult↗

"Hemicrania episodica"--a new type of headache or a pre-chronic stage of hemicrania continua?

For seventeen years, a young man suffered from headaches of one to three days duration occurring once every six or seven days and totally disappearing between episodes. These were strictly unilateral (always on the left side), and were absolutely responsive to indomethacin. They differ clinically from the other two indomethacin-responsive headaches described up to now: Hemicrania Continua (HC) and Chronic Paroxysmal Hemicrania (CPH). He has a sister suffering from HC. Similar to HC, but unlike CPH, topical tyramine in our patient's eyes resulted in anisocoria before, but not after, indomethacin treatment. Our case differs from HC, however, in its time pattern; it could either be a pre-chronic stage of HC or a new type of headache. It seems unlikely that a time pattern that has remained unchanged for 17 years will become continuous, as in HC, in the future, and thus it is possible that our patient represents a case of a new type of headache that we propose to name "Hemicrania Episodica." In any case, it seems probable that this type of headache, although clinically different, may share a common pathogenic basis with HC.

Adult↗

Naltrexone versus acamprosate: one year follow-up of alcohol dependence treatment.

Naltrexone and acamprosate reduce relapse in alcohol dependence. They have not yet been compared in a published trial. The aim of this study was to compare the efficacy of these compounds in conditions similar to those in routine clinical practice. Random allocation to a year of treatment with naltrexone (50 mg/day) or acamprosate (1665-1998 mg/day) was made in 157 recently detoxified alcohol-dependent men with moderate dependence (evaluated using the Addictions Severity Index and Severity of Alcohol Dependence Scale). All were patients whom a member of the family would accompany regularly to appointments. Alcohol consumption, craving and adverse events were recorded weekly for the first 3 months, and then bi-weekly, by the treating psychiatrist who was not blinded. At 3-monthly intervals, investigators who were blinded to the treatment documented patients' alcohol consumption based on patients' accounts, information given by the psychiatrists when necessary, and reports from patients' families. Serum gamma-glutamyltransferase (GGT) was also measured. Efforts were made to sustain the blindness of the investigators. The same investigator did not assess the same patient twice. The integrity of the blindness was not checked. There was no difference between treatments in mean time to first drink (naltrexone 44 days, acamprosate 39 days) but the time to first relapse (five or more drinks in a day) was 63 days (naltrexone) versus 42 days (acamprosate) (P = 0.02). At the end of 1 year, 41% receiving naltrexone and 17% receiving acamprosate had not relapsed (P = 0.0009). The cumulative number of days of abstinence was significantly greater, and the number of drinks consumed at one time and severity of craving were significantly less, in the naltrexone group compared to the acamprosate group, as was the percentage of heavy drinking days (P = 0.038). More patients in the acamprosate than the naltrexone group were commenced on disulfiram during the study. Naltrexone patients attended significantly more group therapy sessions, though this could not explain their better outcome. There were non-significant trends for the naltrexone group to comply better with medication, to stay in the study longer, and to show greater improvement over baseline in serum GGT.

Acamprosate↗

[Prescription patterns of older and newer antidepressants for geriatric depressive out-patients].

OBJECTIVE: To study the prescription patterns of antidepressants for an elderly population. METHODS: 140 out-patients suffering an index depressive episode were studied and followed for at least one year. RESULTS: Demografics: 75% women. Mean age: 72.4%. Mayor depression: 71%. Late-onset: 41%. The most frequently used types the frist choice were SSRIs (48.6%) and Tricyclics (45%), the molecules initially most prescribed: Fluoxetine (26%), Mianserin (13%) and Paroxetin (10%). Initial choice of treatment achieves satisfactory remission in 32.9% of the cases. 57% of patients needed a frist malecule switch, 23% received only two molecules, 16% three, 5% four and 11% five molecules or more. After the first switch, the initial SSRI was substituted by another SSRI in 48% of the cases and by a Tricyclic in 30%. Initial Tricyclic chaged to a SSRI in 33% and another Tricyclic in 45%. The patterns of Tricyclics and SSRIs use were not essentially different and both were used globally in the same proportion, although the most prescribed molecules were Fluoxetine, Fluvoxamine and Paroxetine. Both groups achieved statistically similar number of remissions and suppressions by intolerance or ineficcacy but tricyclics were increasingly used from the frist switch onwards.

Age Factors↗

[Validation in the adult Spanish population of the Wender Utah Rating Scale for the retrospective evaluation in adults of attention deficit/hyperactivity disorder in childhood].

INTRODUCTION: Attention Deficit/Hyperactivity Disorder (ADHD) is one of the most common neuropsychiatric disorders in the early ages. Recently, it has been verified that presence of ADHD in early ages could be a vulnerability factor for developing different psychiatric disorders in adults, such as substance abuse and personality disorders. The retrospective diagnosis of this disorder in early ages of adult patients is specially problematic. OBJECTIVE: The Wender Utah Rating Scale (WURS) has been translated and adaptated with the purpose of validating it in the Spanish population. PATIENTS AND METHOD: It was administered the questionnaire to 266 patients of an Addictive Behaviours Unit. In 82 cases it was realized a clinical diagnosis of ADHD in early ages, and others 184 cases did not show antecedents of this disorder. RESULTS: 25 items which better discriminate cases from controls were chosen. The Cronbach s coefficient for this subscale was 0.94. The cut off 32 optimized sensitivity (91.5%) and specificity (90.8%). The positive and negative predictive values was 81% and 96% respectively. The total of incorrectly classified subjects was 9%. CONCLUSIONS: Our version of the WURS shows an adequate psychometric characteristics, that indicate an adequate validity for the detection of adult patients with antecedents of ADHD in early ages. In our population of patients with addictive behaviours, it has demonstrated to be very useful to differentiate an important subgroup of patients with antecedents of ADHD in early ages. It would be very interesting the replication of this study in other psychopathological and neurological conditions.

Adult↗

[Efficacy of naltrexone in the treatment of alcohol dependence disorder in women].

UNLABELLED: Alcoholism is a major public health problem. Although its prevalence is higher in men, the clinical and social repercussions of alcoholism in women are also of great concern, as they have differential characteristics in different vulnerability, and thus therapeutic implications. In recent years, we have seen an increase of the percentages of women with problems related to alcohol consumption in Spain. Several pharmacological treatments as the antagonist of the opioid receptors naltrexone have demonstrated efficacy in the treatment of dehabituation of alcoholism in males, however, there are no studies in the female population. This report is the first randomized study about the efficacy of naltrexone in the treatment of dehabituation in women with alcohol dependence disorder. METHODS: In a 12 week, single-blind, randomized trial, we studied 100 women with alcohol dependence disorder (DSM-IV), evaluating the efficacy of adding naltrexone as adjunctive treatment to the dehabituation treatment. RESULTS: The naltrexone group showed a lower rate of alcohol relapse during the follow-up period (76 % vs. 46%; chi2=8.239; p=0.004), and significantly lower dropout rates (16% vs. 38 %; chi2=5.074; p=0.024). We also found a lower number of days of intoxication (2.88 vs. 14.64; t=2.732; p=0.011). CONCLUSIONS: Naltrexone shows efficacy as adjunctive treatment to maintain abstinence in women with alcohol dependence disorder. Further studies are needed to confirm the efficacy of this treatment and to find specific predictors of good outcome in women.

Adult↗

[Oxcarbazepine in the prevention of epileptic syndromes in alcohol detoxification].

INTRODUCTION: Alcohol withdrawal syndrome may be accompanied by severe complications, such as epileptic syndromes or delirium tremens. A number of pharmacological strategies, especially benzodiazepines (BZD), have been used in their treatment and prevention, although problems can arise from the use of these drugs due to their addictive properties. The classical anticonvulsive drugs are rarely employed as an alternative because of their side effects, but the latest generation of substances could be especially useful. AIMS. The aim of this study was to examine the safety of oxcarbazepine (OXC) in the prevention of epileptic seizures and complications deriving from the withdrawal syndrome in alcohol detoxification treatment. PATIENTS AND METHODS: The study involved a comparison of two groups of patients with a syndrome of physical dependence on alcohol, 42 of whom were treated with OXC and the remaining 42 received BZD as part of a programmed detoxification therapy. RESULTS: Both OXC and BZD were equally efficient in preventing the appearance of epileptic complications and in reducing withdrawal symptoms. Overall, OXC produced fewer adverse events (p < 0.001) and offered fewer problems when it came to ending administration (p < 0.001). CONCLUSIONS: OXC can be a valuable alternative to BZD and other pharmacological treatments in the prevention of complications in detoxification therapy, especially because of the absence of addictive properties and its having a better safety profile than classical anticonvulsant drugs.

Adult↗