Dissociation of the effects of ethanol on memory, anxiety, and motor behavior in mice tested in the plus-maze discriminative avoidance task.

RATIONALE: Several studies have shown the amnestic effects of ethanol (ETOH). However, while memory tasks in rodents can be markedly influenced by anxiety-like behavior and motor function, ETOH induces anxiolysis and different effects on locomotion, depending on the dose. OBJECTIVE: Verify the effects of ETOH in mice tested in the plus-maze discriminative avoidance task (PMDAT) concomitantly evaluating memory, anxiety-like behavior, and motor behavior. METHODS: ETOH acutely or repeatedly treated mice were submitted to the training session in a modified elevated plus-maze with two open and two enclosed arms, aversive stimuli in one of the enclosed arms, and tested 24 h later without aversive stimuli. Learning/memory, locomotion, and anxiety-related behavior were evaluated by aversive arm exploration, number of entries in all the arms and open arms exploration, respectively. RESULTS: Acute ETOH: (1) either increased (1.2-1.8 g/kg) or decreased (3.0 g/kg) locomotion; (2) decreased anxiety levels (1.2-3.0 g/kg); and (3) induced learning deficits (1.2-3.0 g/kg) and memory deficits (0.3-3.0 g/kg). After repeated treatment, sensitization and tolerance to hyperlocomotion and anxiolysis induced by 1.8 g/kg ETOH were observed, respectively, and tolerance to the amnestic effect of 0.6 (but not 1.8) g/kg ETOH occurred. CONCLUSION: Neither the anxiolytic nor the locomotor effects of ETOH seem to be related to its amnestic effect in the PMDAT. Additionally, data give support to the effectiveness of the PMDAT in simultaneously evaluating learning, memory, anxiety-like behavior, and motor activity by different parameters. Possible relationships between the behavioral alterations found are discussed.

Association of paradoxical sleep deprivation and ecstasy (MDMA) enhances genital reflexes in male rats.

Ecstasy ((+/-)3,4-methylenedioxymethamphetamine, MDMA) is a psychostimulant and a synthetic derivative of amphetamine that, according to its consumers, promotes the enhancement of sexual pleasure. This study sought to investigate the effects of ecstasy in the genital reflexes of paradoxical sleep deprived (PSD) male rats. Distinct groups of PSD rats were administered with saline or different doses of ecstasy. The incidence of genital reflexes was verified for 100 min. The four doses that were used induced genital reflexes in PSD animals and these significantly differed from their respective treated control groups. Under the influence of two intermediary doses (2.5 and 5mg/kg), all animals displayed erection and ejaculation. The frequency of genital reflexes was also significantly greater than in relation to the PSD-saline group. The comparison between cocaine and ecstasy in PSD rats revealed that ecstasy induced more erections and ejaculations than cocaine. Thus, the present results showed a great enhancement of the genital reflexes of PSD rats that might have occurred due to serotoninergic alterations induced by this illicit substance when associated to sleep deprivation.

Role of learning of open arm avoidance in the phenomenon of one-trial tolerance to the anxiolytic effect of chlordiazepoxide in mice.

A single exposure to the elevated plus-maze (EPM) test of anxiety reduces or abolishes the anxiolytic efficacy of benzodiazepines on a second trial. Some possible explanations to the occurrence of this phenomenon (one-trial tolerance-OTT) involve behavioral modifications thought to be consequence of some kind of learning in the first trial. In the present study, the influence of learning-impairing situations on the effects of the benzodiazepine chlordiazepoxide on mice re-tested in the EPM is investigated. The results showed that: (1) as expected, the administration of chlordiazepoxide to mice re-tested in the EPM- under the same conditions of the first trial- failed to induce anxiolysis; (2) a decreased percent time in the open arms was observed on the second trial of mice exposed to both trials under the same experimental conditions; (3) neither the increase in open arm avoidance by mice re-exposed to the EPM nor the OTT to chlordiazepoxide effect were modified by administration of the amnestic agent scopolamine; (4) the decrement of the duration of the first trial to 1 min or the change in light and noise conditions in both trials counteracted the increase in open arm avoidance on trial 2; (5) none of the later procedures modified the phenomenon of OTT. Although not discarding the modulation exerted by other memory processes in the OTT phenomenon, the results indicate that situations that impair the learned avoidance response to the open arms in the EPM do not modify the phenomenon of OTT.

Role of anxiety levels in memory performance of spontaneously hypertensive rats.

Spontaneously hypertensive rats (SHR) show behavioural differences when compared to their strain-matched controls. These differences include decreased anxiety-like behaviour in SHR, while both improved performance and behavioural deficits have been reported in learning/memory studies. Considering that alterations in anxiety levels during the training session can modify retention performance in animal models of memory, the aim of the present study was to investigate the role of anxiety levels in the performance of SHR rats in the plus-maze discriminative avoidance task (PM-DAT), in which memory and anxiety are evaluated simultaneously. Adult (5-month-old) and young (45-day-old) SHR and normotensive Wistar rats (NWR) were treated with chlordiazepoxide (CDZ) or saline. Thirty minutes later, rats were submitted to the PM-DAT training session. After 24 h, the test session was performed. The results showed that: (1) adult SHR showed lower anxiety levels compared to adult NWR; (2) adult SHR and NWR, as well as young NWR, showed significant retention of the task, while young SHR showed impaired performance; (3) 5.0 mg/kg CDZ decreased anxiety levels in adult NWR and young and adult SHR; (4) 5.0 mg/kg CDZ impaired retention in adult SHR and NWR and increased retention in young SHR. Our data suggest an important role of anxiety levels in the performance of SHR in a plus-maze discriminative avoidance task.

Important role of striatal catalase in aging- and reserpine-induced oral dyskinesia.

Tardive dyskinesia, the most serious iatrogenic movement disorder, has been tentatively associated with nigrostriatal dopaminergic supersensitivity and with oxidative stress. It is also suggested that long-term neuroleptic treatment does not cause oral dyskinesia (OD), but interacts with some substrate of brain aging, resulting in the premature emergence of OD, that can occur spontaneously with aging. In order to investigate a possible role of nigrostriatal dopaminergic supersensitivity and of oxidative stress in aging- and reserpine-induced OD, the stereotyped behavior induced by dopaminergic agonists, a functional index of dopaminergic striatal activity, as well as the striatal antioxidant enzymes glutathione peroxidase and catalase were assessed. We demonstrate that, opposite to normotensive Wistar rats (NWR), spontaneously hypertensive rats (SHR) do not develop aging- or reserpine-OD. There were no differences between NWR and SHR in stereotyped behavior or in striatal glutathione peroxidase activity. Adult and old SHR presented higher striatal catalase activity relative to NWR, and aging increased it only in SHR. The catalase inhibitor aminotriazole reverted the absence of aging- and reserpine-induced OD in SHR. Our results suggest an important role of striatal catalase in the development of reserpine- and aging-induced OD.

Role of hippocampal oxidative stress in memory deficits induced by sleep deprivation in mice.

Numerous animal and clinical studies have described memory deficits following sleep deprivation. There is also evidence that the absence of sleep increases brain oxidative stress. The present study investigates the role of hippocampal oxidative stress in memory deficits induced by sleep deprivation in mice. Mice were sleep deprived for 72 h by the multiple platform method-groups of 4-6 animals were placed in water tanks, containing 12 platforms (3 cm in diameter) surrounded by water up to 1 cm beneath the surface. Mice kept in their home cage or placed onto larger platforms were used as control groups. The results showed that hippocampal oxidized/reduced glutathione ratio as well as lipid peroxidation of sleep-deprived mice was significantly increased compared to control groups. The same procedure of sleep deprivation led to a passive avoidance retention deficit. Both passive avoidance retention deficit and increased hippocampal lipid peroxidation were prevented by repeated treatment (15 consecutive days, i.p.) with the antioxidant agents melatonin (5 mg/kg), N-tert-butyl-alpha-phenylnitrone (200 mg/kg) or vitamin E (40 mg/kg). The results indicate an important role of hippocampal oxidative stress in passive avoidance memory deficits induced by sleep deprivation in mice.

Cisplatin plus epirubicin and etoposide followed by irradiation plus lonidamine in stage III nonsmall cell lung cancer.

Forty-seven patients with stage III nonsmall cell lung cancer (NSCLC) were treated with the sequential administration of combination chemotherapy consisting of cisplatin, epirubicin and etoposide and of irradiation plus lonidamine. The response rate was 49% after chemotherapy with an improvement of 14% after radiation therapy and lonidamine. The median survival was around 15 months for responders and 9 months for nonresponders. Toxicity was moderate and acceptable. It is concluded that this schedule is active in the treatment of NSCLC.

[Lipolysis and ketosis during swimming in thermal water]. / Lipolisi e chetosi nel nuoto in acqua termale.

Plasma free fatty acids, blood glucose, beta-hydroxybutyrate and acetoacetate variations were studied in rats during swimming. Rats were forced to swim for 30 min in thermal water (source of Abano Terme) at 35 degrees and in normal water at 25 degrees. During swimming in thermal water plasma free fatty acids were increased, the glycemia remained unaffected, the beta-hydroxybutyrate and acetoacetate decreased. The swim in normal water induced a sharp increase of plasma free fatty acids, a decrease of blood glucose, an increase of blood beta-hydroxybutyrate and a marked decrease of acetoacetate. From these data, some indications of clinical interest are presented and discussed.

[Beneficial effect of swimming in thermal waters on muscle glycogen depletion]. / Benefico effetto del nuoto in acqua termale sulla deplezione del glicogeno muscolare.

The effect of swimming in the termal water on muscle glycogen stores was studied. After 30 min the muscle glycogen results in a diminution, but it is not depleted. On the contrary, 30 min of swimming in normal water results in a depletion of muscle glycogene stores. The glycemic homeostasis is well maintained in thermal water, and hypoglicemia occurs only after swimming in normal water.

Effect of swimming in thermal water on skeletal muscle, liver and heart glycogen.

Skeletal muscle, liver and heart glycogen variations, induced by swimming in thermal water (at 35 degrees C) as a model of physical exercise for clinical use, were studied. Muscle and liver glycogen moderately decreases after a 30-min period of swimming and comes near to depletion after 60 min. Heart glycogen decreases only slightly after 60 min. Blood glucose and plasma insulin decrease only after 60 min of swimming. A 30-min swim in thermal water, cooled to 25 degrees C, depletes muscle and liver glycogen and slightly decreases heart glycogen. Under these conditions, plasma insulin decreases and hypoglycemia occurs. The results seem to indicate some advantages of swimming in hot thermal water in order to prevent glycogen store depletion as the physiological prerequisite for a physical exercise of clinical interest to obtain therapeutical benefits, avoiding premature fatigue and exhaustion.

Six-drug sequential chemotherapy in non small cell lung cancer. A North Milan Group Study.

Forty-five patients with inoperable non small cell lung carcinoma were treated according to a sequential polychemotherapeutic regimen with cisplatin-vinblastine (A), cyclophosphamide-etoposide (B), and adriamycin-vincristine (C). Patients were evaluated every two cycles. Ten patients (22.2%) showed a partial response with a mean duration of 20 weeks, and mean survival of 50.8 weeks. It is remarkable that, among them, 6 patients (13.3%) lived over 12 months and three (6.6%) over 18 months. The mean survival for all patients was 35.7 weeks. Toxicity was acceptable and reversible.

Dental extraction in congenital hemorrhagic patients.

125 dental extractions were performed in patients with hemophilia A, B, von Willebrand disease and rare coagulopathies. The missing factor was brought to a level of 15-40% according to the degree of surgical trauma. In the majority of cases a single pre-extraction administration of concentrate was sufficient. Antifibrinolytics were administered to the patients (tranexamic acid, 60 mg/kg/day) for 8-10 days. After tooth extraction, a fibrin sponge was positioned using anti-traumatic cross suture. In 90% of cases there was no bleeding, in the others modest easily controllable hemorrhagic episodes. Our results show that it is sufficient in hemophilia A and B to use low doses of antihemophilic concentrate (10-20 U/kg) and frequently a single pre-extraction administration. In rare coagulopathies the hemostatic procedure and dental management have also to be similar to those used in hemophilia A and B.

[Clinico-experimental study of a new antibactorial agent for local use in stomatology]. / Contributo clinico-sperimentale allo studio di un nuovo antibatterico per uso locale in stomatologia

Tibezonium iodide is a new drug having antibacterial activity for the therapy and the prevention of mouth infections. Before testing its therapeutic efficacy, its effect on the bacterial flora of the human saliva was verified as follows. Salivary samples, collected before and after the administration (double-blind, cross-over) to volunteers, were counted for bacteria. The drug reduced the bacterial count in the saliva with statistical significance in both the pharmaceutical forms. Subsequently the drug was tested in different dental or oral conditions. To 90 patients suffering from marginal paradentitis or other diseases with this type of complications tablets were administered. The results obtained in this group were satisfactory or almost satisfactory in 73.5% of the cases examined. The patients treated with bubble-gums were 70. All of them were suffering from the same kind of disease of the first group; a few of them had alveolitis following tooth extraction. The results in these subjects were satisfactory or almost satisfactory in 77% of the cases examined. Tibezonium proved to be particularly effective in marginal paradentitis and in piorrhoic paradontosis. Bubble-gums should not be used in subjects with dental mobile prosthesis.