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Cannabidiol (CBD), the main non-psychoactive component of Cannabis sativa L., is widely used in therapy for the treatment of different diseases and as an adjuvant drug. Our aim was to assess the effects of CBD on proinflammatory cytokine production and cell proliferation in human peripheral blood mononuclear cells (PBMCs) and on CD4+ T lymphocyte differentiation, and, furthermore, to test CBD's ability to affect the functional properties of regulatory T cells (Treg). Experiments were performed on isolated PBMCs and purified CD4+ T lymphocytes obtained from the buffy coats of healthy subjects. Cytokines produced by CD4+ T cells were evaluated by flow cytometry and intracellular cytokine staining techniques. PBMC cytokine production was measured by an ELISA assay. Real-time PCR was used to assess the mRNA expression of cytokines and the key transcription factors (TFs) of CD4+ T cells. Finally, the proliferation of PBMC and CD4+ T effector cells (Teff), alone and in the presence of Treg, was assessed by flow cytometry. Results showed that CBD affects both the frequency of IL-4-producing CD4+ and of IFN-γ/IL-17-producing cells and dramatically decreases the mRNA levels of all TFs. Stimuli-induced cytokine mRNA expression was decreased while protein production was unaffected. CBD was unable to affect the ability of Treg to prevent Teff cell proliferation while it slightly increased PBMC proliferation. In conclusion, CBD may inhibit the expression of proinflammatory cytokines; however, the effect of CBD on cell proliferation suggests that this cannabinoid exerts a complex activity on human PBMCs and CD4+ T cells which deserves further investigation.

Genetic risk factors seem to play a role in sporadic Parkinson's disease (PD), maybe triggering oxidative stress and excitotoxicity within substantia nigra. However, genetic factors act at systemic level: reduced activity of mitochondrial enzymes and decreased glutamate uptake have been shown in platelets from PD patients. In this study we investigated glutamate uptake in platelets from 38 sporadic PD patients, 13 patients with parkinsonian syndromes and 28 controls and assessed polymorphisms of alpha-synuclein and ApoE genes. A 48% reduction of glutamate uptake p)<0.0001) was observed in PD patients which, with respect to control groups, correlated with the disease severity (r = -0.44, p < 0.05). Genetic studies of this population did not show differences between PD and controls, nor correlations with platelet glutamate uptake.

Background: We investigated whether a new non-benzodiazepine anti-anxiety drug, alpidem, produces weaker withdrawal symptoms than alprazolam., Method: Under a double-blind procedure, 122 patients suffering from general anxiety disorders were randomly allocated to either alpidem (50 mg, three times a day) or alprazolam (0.5 mg, three times a day) for six weeks, followed by a two-week placebo withdrawal phase. The diagnosis of withdrawal syndrome (WS) was made, in blind conditions, on the basis of the Withdrawal Symptom Check List (WSCL), after one or two weeks of discontinuation of active treatment., Results: The WS occurred significantly less frequently in the alpidem group (n = 10, 18%) than in the alprazolam group (n = 26, 48%). Typical withdrawal symptoms on the WSCL were also significantly less severe (P = 0.044) in the alpidem group compared with the alprazolam group., Conclusions: Alpidem may be a valid alternative to current benzodiazepine anxiolytic therapy because it produces fewer and weaker withdrawal symptoms than alprazolam and is better tolerated.

The efficacy and safety of alpidem, a new anxiolytic imidazopyridine, were compared with those of placebo in anxious elderly patients (65-80 years) by means of a randomized, double-blind, parallel group study. Following a 7-day "placebo run-in," 40 anxious patients were randomized to receive either alpidem or placebo. Daily doses ranging from 75 to 150 mg (25-50 mg t.i.d.) were administered for 3 weeks. Hamilton Rating Scale for Anxiety (HRSA), State Trait Anxiety Inventory (STAI-X1), Visual Analogue Scale (VAS), and Clinical Global Impression (CGI) were used on days 0, 3, 7, 14, and 21 for assessing efficacy. Psychomotor and mnesic performances were evaluated at the same time by means of the Digit Symbol Substitution Test (DSST), the Grünberger's test for fine motor coordination, and the Hawie's test for immediate memory. Possible adverse events were also recorded during the five visits. The anxiolytic efficacy of alpidem was significantly (p < 0.01) superior to that of placebo in all the rating scales adopted. The anxiolytic action was clearly evident from day 7. For most of the patients the active dose was 25 mg t.i.d. No relevant adverse effects were observed in both groups. No impairment of psychomotor and mnesic performances could be observed in the alpidem group. Alpidem is a new interesting anxiolytic drug for anxious elderly patients because it appears remarkably safe and, at effective doses, it does not impair psychomotor performances and cognitive functions.

The F-wave velocity in the central segment (axilla to spinal cord) was studied employing the "collison technique" described by Kimura (1974), and compared with the conduction velocity obtained with the usual methods. In 25 normal subjects the F-wave velocity increased proceeding proximally, reaching the maximum values in the central tract (64.86 +/- 2.23 m/sec in ulnar nerve). In 11 patients affected by motor neurone disease and 11 patients affected by amyotrophic lateral sclerosis the F-wave velocity decreased significantly proceeding proximally and the minimum values were found in the central tract (52.51 +/- 2.15 m/sec in MND and 48.64 +/- 5.60 m/sec in ALS). We therefore suggest the use of F-wave velocity as a more complete element for precise localization of the lesion in the central segment when the motoneurone is primarily involved.

Nightly EEG recordings were performed in 8 healthy volunteers after intramuscular injections of placebo and 30 mg vincamine, under double-blind conditions, according to a crossover design. The single dose of vincamine induced a significant decrease in sleep Stage 4, a decrease in REM stages which approached statistical significance, and finally an increase in REM latency only in subjects showing low baseline values of this parameter. The above data confirm the awakening and antidepressant action of vincamine observed in previous studies in both animals and man.

A double-blind, randomized electromyographic investigation was conducted of the effects of cerebral ganglioside treatment on patients suffering from diabetic or alcoholic polyneuropathy. Cerebral gangliosides (50 mg once a day) administered to 15 diabetic and to 15 alcoholic neuropathic patients for 40 days, facilitated the reappearance of sensory potentials and significantly increased the MAP amplitude in median, ulnar, and peroneal nerves. In relation to ganglioside treatment, there was no significant change in the conduction velocities or in the distal latencies of these nerves, nor was there a change in the duration of the MAPs. On the basis of these results, it is suggested that the cerebral gangliosides are capable of inducing an improvement in the excitability of nerve fibers and of facilitating the processes of reinnervation, probably by means of an enhancement of fiber sprouting.

Twenty patients suffering from transient attacks of ischaemia were studied. Seven received acetylsalicylic acid, six dipyridamole and seven a combination of the two drugs. No significant difference in platelet aggregation was shown in the acute phase between the three treatment groups using an adenosine diphosphate test method. Using Thrombofax platelet substitute, however, a significant difference was seen in all measures. On the seventh day following the ischaemic attack the Thrombofax values returned to normal but, in contrast, Platelet Factor 4 release was increased. Monthly testing of platelet activity during treatment shows that the combination of acetylsalicylic acid with dipyridamole was more effective in bringing about an early inhibition of Platelet Factor 4 release than either agent alone.

A case of thyrotoxicosis associated with neuropathy and encephalomyelitis is reported which gradually improved as regards the hyperthyroidism and the neurological deficit during treatment with Tapazole. The possible role of the nervous system of an excess of thyroxine or an autoimmune factor as a cause of the involvement is discussed.

Lymphocytes of twenty-seven patients with polymyositis were incubated in vitro with cholinergic receptor rich membranes obtained from the electric organs of Torpedo Marmorata. Lymphocytes of polymyositic patients were slightly stimulated; positive responses were present mainly in patients affected from more than a year. Sensitization against the nicotinic cholinergic receptor may explain the occurrence of the myasthenic syndrome with polymyositis.

The observation of a patient suffering from a parkinsonian syndrome, almost entirely expressed on the right side, and "on-off" attacks with rotatory movement of the trunk, led us to consider that the rotational model of animals may be reproduced in man. The symptoms presented by our patient may reflect a predominant degeneration in the nigrostriatal pathway of the left side. We suggest that his torsion behavior is due to hypersensitivity phenomenon of the dopaminergic receptors on this side.

The anxiolytic activity of alpidem (150 mg/day) and its effects on psychomotor performances were compared with placebo in 60 outpatients. The trial was a double-blind, parallel group, and the two treatments were administered orally in three divided doses for 3 weeks. Eighteen male and 42 female patients (mean age, 39.6 years) suffering from generalized anxiety or adjustment disorder with anxious mood of at least 1-month duration entered the trial at the end of a 1-week placebo run-in period designed to exclude early placebo responders. Efficacy was assessed with the Hamilton rating scale for anxiety (HRSA), the state-trait anxiety inventory (STAI x 1: anxiety as state), a visual analogue scale (VAS), and clinical global impression (CGI). Psychomotor performance was assessed by the digit symbol substitution test (DSST). Alpidem was significantly more effective than placebo in decreasing the severity of anxiety, both in the physician's judgment [total HRSA (p = 0.007), psychic symptoms (p = 0.0040), somatic symptoms (p = 0.0002)] and in the patients' evaluation [STAI x 1 (p = 0.0001) and VAS (p = 0.0003)]. Psychomotor performance was improved by both treatments; there was no difference between results with alpidem and placebo at the DSST (p = 0.2801), but the improvement was almost twofold on alpidem. Side effects were negligible with both treatments and the efficacy index, obtained from the CGI, was significantly better with alpidem than with placebo after day 7 (at least p less than 0.03).

Sleep induction has been studied in humans after the administration of apomorphine, a direct stimulant of the central dopaminergic system. The drug induced sleep and vomiting in healthy volunteers while it had no significant effect on 10 Parkinsonism patients treated for a long period with L-dopa. Apomorphine given to a group of Parkinsonism patients not receiving any specific treatment, and with a lower degree of disease severity, induced vomiting and sleep with a pattern similar to that in healthy subjects. A relationship between the dopaminergic system and sleep induction is suggested.

Transdihydrolisuride is an ergot derivative with mixed agonist and antagonist effects on central dopamine receptors. We gave the drug orally (1 mg daily) to 10 patients with Huntington's disease. In seven patients, the chorea improved with no adverse effects during the study.

The authors studied the effects of lisuride hydrogen maleate (lisuride) on the hyperkinesias of 11 patients suffering from Huntington's chorea (HC). In all patients, acute injection of 150 micrograms of the drug induced a marked temporary improvement of the abnormal involuntary movements; the favourable drug-effect was more pronounced in the patients with a less severe degree of hyperkinesia. The antichoreic activity of the drug was prevented by pretreatment with haloperidol (2 mg) or sulpiride (400 mg), both injected intramuscularly 30 min before lisuride administration. The authors suggest the improvement of the motor disturbance induced in HC by lisuride may be explained on the basis of its preferential action on a subset of brain dopaminergic receptor.

A double-blind, double-dummy clinical trial was conducted in which the efficacy of cyclandelate 1600 mg daily was compared with that of flunarizine 10mg daily in 40 patients (25 men and 15 women) with dementia of cerebrovascular origin. Parameters were assessed before treatment, and after 45 and 90 days of therapy. At 90 days, significant improvements were observed in patients given cyclandelate in measurements of P100 latency in the left eye, neurological impairment, dementia scores, ischaemia scores, Gottfries mental deterioration scale, Hamilton depression scores, short term visual memory, long term memory, Bender-Gestalt test and Koh's blocks test. In flunarizine recipients, improvements were observed in neurological impairment, ischaemia scores, Gottfries scale and Hamilton depression scores. Patients treated with cyclandelate showed significantly greater ameliorations in symptoms as assessed by the ischaemia scale, evoked visual potential, visual memory and Koh's block test compared with those given flunarizine. However, in none of the parameters was flunarizine superior to cyclandelate.

Histochemical, biochemical and electromyographic studies were performed in a case of carnitine deficiency in serum and in muscle. Clinical features include proximal muscle weakness, predominant type I fiber impairment, excess of triglycerides and moderate glycogen accumulation in muscle. No abnormalities of palmityl CoA synthetase, carnitine palmityl transferase, carnitine acetyl transferase and lipase were evidenced. An interesting EMG decremental pattern was recorded. Correlations between electromyographic and biochemical findings are considered. A clinical improvement, a normal plasma carnitine level and a normal response at EMG repetitive stimulation were found after carnitine treatment.

A prospective study of 93 acute stroke patients randomly selected by type of antiedema treatment given (hypertonic glicerol infusion plus dexamethasone versus dexamethasone alone) failed to elicit any statistically significant difference between the two treatments on survival rates and quality of survival 7 and 30 days after the stroke.

In this study the effects of an acute injection of lisuride and apomorphine in 12 subjects affected by dystonic-dyskinetic syndromes of different aetiology are evaluated: 3 patients with spasmodic torticollis, 4 with tardive dyskinesia and 5 Parkinson patients suffering from "on-off" attacks with prominent dyskinesias during the mobile phase. In the last group drugs were administered during the "on" phase. In 11 out of 12 patients both lisuride and apomorphine induced a marked improvement of the abnormal involuntary movements. In Parkinson and torticollis patients both drugs also reduced the rigidity. In comparison to apomorphine, lisuride showed a more effective and long-lasting action. Only in one Parkinson patient did the drugs fail in showing any change.