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Biomedical subjects

G Colombo

Publications and source records attributed to G Colombo.

At least 37 records · Page 2Linked to original sources

Appetite suppression and weight loss after the cannabinoid antagonist SR 141716.

The effect of the cannabinoid CB1 receptor antagonist, SR 141716, on food intake and body weight was assessed in adult, non-obese Wistar rats. The daily administration of SR 141716 (2.5 and 10 mg/kg; i.p.) reduced dose-dependently both food intake and body weight. Tolerance to the anorectic effect developed within 5 days; in contrast, body weight in SR 141716-treated rats remained markedly below that of vehicle-treated rats throughout the entire treatment period (14 days). The results suggest that brain cannabinoid receptors are involved in the regulation of appetite and body weight.

Animals

Gamma-hydroxybutyric acid intake in ethanol-preferring sP and -nonpreferring sNP rats.

Gamma-hydroxybutyric acid (GHB) and ethanol share several pharmacological similarities, suggesting that GHB may exert ethanol-like effects in the central nervous system. The present study was designed to test whether selectively bred ethanol-preferring rats would, unlike ethanol-nonpreferring ones, self-administer GHB, consistent with their higher preference for ethanol. Male ethanol-naive Sardinian alcohol-preferring (sP) and Sardinian alcohol-nonpreferring (sNP) rats were used. In Experiment 1, GHB solution (1% (w/v) in water) was initially offered as the sole fluid available for 14 consecutive days and then presented under the two-bottle, free-choice regimen, one bottle containing water and the other the GHB solution, for an additional 14 consecutive days. During the free-choice phase, high preference for GHB and intake of pharmacologically relevant daily doses of GHB developed in both rat lines, presumably because the 14-day no-choice period would unmask the reinforcing properties of GHB and lead to acquisition of GHB preference also in the supposedly less susceptible sNP rats. In Experiment 2, the forced GHB drinking phase was reduced to 3 days. Under the subsequent free-choice regimen, daily GHB preference and intake were initially low in both sP and sNP rats; however, after approximately 10 days, GHB preference and intake in sP rats rose progressively and then stabilized to significantly higher levels than in sNP rats throughout the entire free-choice phase. It is likely that episodic binges of GHB intake occurring during the first 10 days resulted in experiencing the reinforcing properties of GHB by sP but not sNP rats. The results of the present study suggest that a) sP rats are genetically more sensitive to the reinforcing effects of both ethanol and GHB than sNP rats; and b) disclosure of the higher sensitivity of sP rats to the reinforcing effects of GHB is a function of the length of the induction procedure. The results are also discussed in terms of differences in GHB receptors contributing to the predisposition to ethanol preference and avoidance, respectively.

Alcohol Drinking

Preprotachykinin-A gene expression in the forebrain of Sardinian alcohol-preferring and -nonpreferring rats.

Increasing evidence suggests that TKergic mechanisms might play a role in ethanol intake control. Preprotachykinin-A (PPT-A) mRNA brain levels were measured in Sardinian alcohol-preferring (sP) and Sardinian alcohol-nonpreferring (sNP) rats. PPT-A mRNAs were about 50% lower in sP than in sNP rats in the bed nucleus of the stria terminalis (BNST), whereas levels in the olfactory tubercle (Tu) were about 30% higher in sP than in sNP rats. Our findings suggest that altered PPT-A gene expression might contribute to the different ethanol preference and intake of sP opposite to sNP rats.

Alcohol Drinking

Locomotor capacity and recovery of spinal cord function in paraplegic patients: a clinical and electrophysiological evaluation.

Recent studies have shown that a locomotor pattern can be induced and trained into paraplegic patients under conditions of body unloading using a moving treadmill. The present study investigated the behaviour of the locomotor pattern and also the relationship of its development to the spontaneous recovery of spinal cord function assessed by clinical and electrophysiological (tibial nerve somatosensory evoked potentials and motor evoked potentials) examinations. The earliest time that spinal locomotor activity could be induced was when signs of spinal shock had disappeared. This activity was distinct from spinal stretch reflex activity. In complete and incomplete paraplegic patients an increase of gastrocnemius electromyographic activity occurred during the stance phase of a step cycle with daily locomotor training over the whole training period of 12 weeks. This was coincident with a significant decrease in body unloading. In contrast to this, neither clinical nor electrophysiological examination scores improved after the onset of training in both patient groups. Only in incomplete paraplegic patients was there an insignificant increase in sensory and motor scores obtained in the neurological examination during the time period before onset of training. An improvement of locomotor function by training was also seen in patients with paraplegia due to a cauda lesion. Therefore, in patients with a spinal cord lesion training effects on muscles and tendons are present in addition to those on the spinal locomotor centres. The findings of this study may be relevant for future clinical treatment of paraplegic patients.

Adolescent

Locomotor training in paraplegic patients: a new approach to assess changes in leg muscle EMG patterns.

This study describes an amplitude independent assessment of changes in leg muscle EMG patterns in both complete and incomplete paraplegic patients during the course of locomotor training. The approach expresses the change as an approximation of the patients' gait EMG pattern compared with that of healthy subjects. The variation ratio (VR), coefficient of variation (CV) and Pearson's correlation coefficient (R), are used as measures of the dissimilarity/similarity of a set of wave forms. These parameters were evaluated for their ability to assess changes in the EMG pattern of the patients with respect to that of healthy subjects. The VR showed the best correlation to our data and was therefore considered to represent the optimum variable in the assessment of changes in EMG patterns.

Adult

Stumbling reactions in man: influence of corticospinal input.

The aim of this study was to evaluate the degree of contribution of supraspinal input to the generation of the compensatory leg muscle activation following stance perturbation. Therefore, evoked motor response (EMR) input-output relations of two different motor tasks were compared at 3 distinct periods: (1) the basic period of muscular activity during standing, i.e. when no additional cortical or spinal activity due to the different tasks is to be expected, (2) the pre-movement period with low background activity, when different spinal and cortical inputs to the motoneuronal pool can be assumed and (3) the period of plateau EMG activity of compensatory and voluntary motor task. Transcranial magnetic stimulation (TMS) just below the motor threshold was applied randomly at 19 different time-intervals before and during the onset of stance perturbation and for comparison during an equivalent voluntary foot-dorsiflexion task. Recordings of electromyographic (EMG) activity from the tibialis anterior (TA) and corresponding ankle-joint movements were made from both legs. Forward-directed displacements were induced by randomly-timed ramp impulses of constant acceleration upon a moveable platform. For comparison, leg muscle EMG was recorded during isometric foot dorsiflexion during stance while leaning back against a support. The stance perturbations were followed by a compensatory response (CR) in the TA with a mean onset time of 81 ms. During the basic period of muscular activity and the period of plateau EMG activity there was no significant difference of the input-output relation between stance perturbation and the voluntary motor task. However, in the voluntary task compared with the CR, there was significantly greater input-output relation (facilitation) of the EMR in the TA following TMS, which may be related to an increased cortical influence. In contrast to this result of the CR following stance perturbation, a facilitation of the EMR was described for hand muscles under corresponding conditions of automatic compensation for muscle stretch, suggesting a transcortical reflex loop. This difference in the results from upper and lower extremity muscles favors the assumption of a predominantly spinal generation of the TA-CR following stance perturbation.

Adult

Locomotor pattern in paraplegic patients: training effects and recovery of spinal cord function.

Recent studies have shown that a locomotor pattern can be induced and utilized by paraplegic patients under conditions of body unloading using a moving treadmill. The present study investigated the behaviour of the locomotor pattern and also the relationship of its development to the spontaneous recovery of spinal cord function assessed by clinical and electrophysiological (tibial nerve somatosensory evoked potentials and motor evoked potentials) examinations. The earliest time that spinal locomotor activity could be induced was when signs of spinal shock had disappeared. This activity was distinct from spinal stretch reflex activity. In complete paraplegic patients the locomotor pattern improved spontaneously without training. This was coincident with both an increase of gastrocnemius electromyographic activity during the stance phase of gait and a decrease of body unloading. These effects reached a plateau after about 5 weeks. In complete and incomplete paraplegic patients a near linear increase of gastrocnemius electromyographic activity occurred during the stance phase of a step cycle with daily locomotor training over the whole training period of 12 weeks. This was also coincident with a significant decrease of body unloading. In contrast to this, neither clinical nor electrophysiological examination scores improved after the onset of training in both patient groups. Only in incomplete paraplegic patients was there recovery, albeit statistically insignificant, of spinal cord function according to the sensory and motor scores obtained in the neurological examination during the time period before onset of training. An improvement of locomotor function by training was also seen in patients with paraplegia due to a cauda lesion. Such training effects on muscles and tendons could be separated from those on the spinal locomotor centres. The findings of this study may be relevant for the future clinical treatment of paraplegic patients.

Adolescent

[Usefulness of stress echocardiography in the diagnosis of syndrome X].

Syndrome X is a clinical entity not yet well defined. The identification of patients with syndrome X is important as, in comparison with patients with obstructive coronary artery disease, their prognosis is quite favorable. The diagnosis is confirmed by coronary angiography, but non-invasive tools can give some useful information, too. We illustrate 5 cases of syndrome X in which the diagnosis, confirmed by coronary angiography, was suspected on the basis of stress echocardiography. We considered 5 female patients, aged 49-65 years, whose exercise electrocardiogram showed signs of reduced coronary reserve. In 3 patients thallium-201 myocardial scintigram was also performed, showing areas of reduced myocardial perfusion in all cases. We suggest the use of stress echocardiography, particularly with dipyridamole, whenever the clinical conditions contrast with the results of exercise ECG.

Aged

Asthma and panic attacks.

Panic disorder (PD) and asthma share many common characteristics and have been found in epidemiological studies to be significantly comorbid. To investigate possible reasons for this overlapping, the authors evaluated 51 patients with asthma, assessing the prevalence of PD and sporadic panic attacks, the temporal relationship between these two disorders, and the familial risk for PD in the families of asthmatics. The results showed significantly higher prevalences of PD, sporadic panic attacks, and social phobia in asthmatics than those reported for the general population. In 9 (90%) of the asthmatics with PD, asthma appeared first. Finally, the morbidity risk for PD in families of asthmatics with PD (13.5%) was significantly higher than in families of asthmatics without evidence of panic (2%). Our results suggest that the high prevalence of PD in asthmatics might be related to a facilitating effect of asthma on the development of PD in subjects with familial predisposition to PD.

Adult

Characterization of the ethanol-like discriminative stimulus effects of 5-HT receptor agonists as a function of ethanol training dose.

A drug discrimination procedure was used to characterize the ethanol-like effects of a variety of 5-HT1 agonists. Previous studies found that the degree of substitution of the 5-HT1B/2C agonist TFMPP (m-trifluoromethylphenylpiperazine) depended on the training dose of ethanol. The present studies extend this initial finding to four additional 5-HT agonists with different selectivity for 5-HT1A, 5-HT1B, or 5-HT2C receptors: CGS 12066B (7-trifluoromethyl-4(4-methyl-1-piperazinyl)-pyrrolo[1,2a]quinoxaline maleate), mCPP [1-(3-chlorophenyl)piperazine diHCl], RU 24969 [5-methoxy-3(1,2,3,4-tetrahydro-4-pyridinyl]-1H-indole succinate and 8-OH DPAT [(+/-)-8-hydroxy-2-(di-n-propylamino)tetralin HBr]. Separate groups of rats were trained to discriminate 1.0 g/kg (n = 7), 1.5 g/kg (n = 6) or 2.0 g/kg (n = 8) ethanol from water. Following training, three to five doses of each 5-HT agonist were tested twice in each rat. The most selective 5-HT1B agonist tested, CGS 12066B (3-17 mg/kg; IP), completely substituted for the 1.0 g/kg ethanol, but not for 1.5 or 2.0 g/kg ethanol. Likewise, the 5-HT1B/2C agonist mCPP (0.56-1.7 mg/kg; IP) completely substituted only in the 1.0 g/kg ethanol training group. The 5-HT1A/1B agonist RU 24969 (0.1-3.0 mg/kg; IP) substituted for all training doses of ethanol, although in a lower proportion of the rats tested in the 2.0 g/kg ethanol training group. Finally, the 5-HT1A agonist 8-OH DPAT (0.1-1.0 mg/kg, IP) did not substitute completely for any ethanol training dose. The results consistently show that agonists with 5-HT1B activity produce discriminative stimulus effects similar to low and intermediate, but not high, ethanol training doses.

Animals

Leg muscle activation during gait in Parkinson's disease: influence of body unloading.

The effect of body unloading (75, 50 and 25% of body weight) on upper and lower leg muscle activation during stepping on a treadmill was investigated in groups of patients with Parkinson's disease and age-matched healthy subjects. The aim of the study was to test the hypothesis that impaired extensor load receptor function exists in the patients. A strong load sensitivity was found for the gastrocnemius (GM) electromyographic (EMG) activity (i.e. EMG amplitude decreased with unloading during stepping in both groups of subjects). The change in the EMG amplitude of the rectus femoris was less dependent upon the load but was observed to be more pronounced in the patients. Upper and lower leg flexor muscles were relatively load-insensitive. The absolute GM EMG amplitude during the stance phase of stepping with normal body loading was significantly smaller in the patients than in the healthy subjects. It is suggested that the latter observation is due to a change in the threshold or bias of the extensor load reflex mechanism in the patients. The slope or gain of this reflex appears to be preserved.

Aged

Radon measurements in the Gran Sasso Underground Laboratory.

Systematic radon monitoring in the Gran Sasso Underground Laboratory was performed in order to determine the background radon contribution to the sophisticated experimental apparatus and to check health physics standards for the personnel. As expected, the radon concentrations were found to depend strongly on the ventilation in the three experimental halls. Considerable reductions in the radon concentrations were obtained in 1993, when fresh air was drawn into the laboratory through a pipe and exhaust air was routed into the highway tunnel.

Air Pollutants, Radioactive

Hand Test scores of panic disordered outpatients sexually abused as children.

A history of childhood sexual abuse has been implicated in a variety of adult psychiatric disorders as more frequent in females than in males and in subjects with more prominent dissociative symptoms such as panic disorder. Previous research has varied greatly in terms of methods, measurement instruments, and reported findings. Recent studies, however, suggest that projective techniques may be useful in resolving some of these inconsistencies. The present study utilized the Hand Test to investigate the late effects of childhood sexual trauma in a group of authenticated cases of panic disordered adult outpatients sexually abused as children compared to a matched sample of presumably nonabused patients. No statistically significant differences on quantitative variables were obtained between the two groups, but the group of outpatients (n = 16) sexually abused as children showed a larger latency to the ninth card of the Hand Test (shock reaction). This may be a potentially useful index in investigating cases of suspected abuse and confirms Wagner's (1983) contention that Card IX has a psychosexual "pull" as documented also by Italian studies.

Adult

New benzamide-derived 5-HT3 receptor antagonists which prevent the effects of ethanol on extracellular dopamine, and fail to reduce voluntary alcohol intake in rats.

A set of substituted benzamides, characterized by the presence of a bulky quinolizidine moiety, were subjected to binding assays for 5-HT3 and D2 receptors on membranes obtained from the bovine area postrema ([3H]-GR65630) and the rat striatum ([3H]-spiperone) respectively. These benzamides resulted unsuitable for the recognition of D2 receptors, while a few of them, devoid of 5-HT4 receptor activity, had consistent affinity for central 5-HT3 receptors, inhibiting also potently the ethanol-induced dopamine efflux from the mesolimbic dopamine terminal region. However they failed in attenuating voluntary alcohol consumption in rats, as observed with several other chemically unrelated 5-HT3 antagonists. Thus the 5-HT3-mediated inhibition of alcohol-induced striatal release of dopamine by substituted benzamides is not a requisite for affecting ethanol intake.

Alcohol Drinking

Diclofenac dispersible provides superior analgesia with faster onset of action compared to naproxen granular in patients with acute, painful, minor sports injuries.

BACKGROUND: To compare the efficacy and tolerability of single doses of diclofenac dispersible and naproxen granular in patients with acute, painful, minor sports injuries. METHODS: Forty-eight adult outpatients with moderate-to-severe pain on movement, following a traumatic event < or = 36 hours previously, participated in this double-blind, between-patient comparative study. Patients were randomised in equal comparative study. Patients were randomised in equal number to receive diclofenac dispersible 50 mg or naproxen granular 500 mg. Pain on movement, pain on pressure, spontaneous pain and pain relief were assessed at 15, 30, 45, 60 minutes and 4 hours after dosing. RESULTS: Both treatments were effective at reducing pain from the 15 minute time point. At 15 minutes there was no significant difference between the treatments for pain on movement (p = 0.4) but diclofenac was significantly superior to naproxen with respect to pain on pressure (p = 0.004), spontaneous pain (p = 0.0022) and pain relief (p = 0.034). In addition, diclofenac was significantly superior to naproxen with respect to AUC0-4 hours for percentage reduction in intensity of pain on movement (p = 0.04) and spontaneous pain (p = 0.0047), and for pain relief scores (p = 0.015). Both treatments were well tolerated. CONCLUSIONS: The study results suggest that diclofenac dispersible 50 mg provides faster and overall better analgesia compared to naproxen granular 500 mg in the acute relief of pain following minor sports injuries.

Acute Disease

Effects of body immersion on postural adjustments to voluntary arm movements in humans: role of load receptor input.

1. The effect of body immersion on postural adjustments was studied in ten healthy subjects. Reaction times, for pushing or pulling a rigid handle, in response to a visual stimulus were measured. In addition EMG recordings were taken from upper arm and lower leg muscles during three levels of body immersion while standing on a platform (immersed to spinal levels: lumbar nerve root 2 (L2); thoracic nerve root 4 (T4); and cervical nerve root 7 (C7)), while floating and while standing or sitting out of water. 2. With increasing levels of body immersion there was a near linear reduction in the amplitude of the gastrocnemius (GM) EMG activity before (200 ms) the onset of a force signal from pulling, but immersion had a significantly weaker effect on the amplitude of the tibialis anterior (TA) EMG during pushing movements. There was no significant difference in the effect of body immersion on biceps femoris (BF) and rectus femoris (RF). Under free-floating conditions postural adjustments did not occur in response to pull or push movements. There were no adaptational changes of EMG adjustments during successive trials at a given immersion level. 3. Under non-immersed conditions reaction times were significantly shorter during sitting than during standing. This difference is assumed to be due to the postural adjustments required while standing before the onset of a voluntary arm movement. While standing, reaction times were significantly longer for pull compared with push movements. Under all conditions of body immersion the reaction times remained longer compared with the sitting condition, even when no leg muscle EMG adjustments were present. 4. It is assumed that the differential effect of body immersion on the antagonistic leg muscles is due to the differential neuronal control of antagonistic leg muscles with a strong influence from proprioceptive input (most probably from load receptors) on the leg extensors. The longer reaction times seen during body immersion, where no postural adjustments were evident, suggests that a supraspinal command to the leg muscles precedes the voluntary arm movement. However, because of the changed/decreased afferent input no postural adjustments are generated.

Arm

T-maze and food reinforcement: an inexpensive drug discrimination procedure.

The present study provides a detailed description of a novel drug discrimination procedure employing a T-maze and food reinforcement. Three groups of rats (n = 5) were trained to run one of the two arms of the maze after the i.g. administration of either 1.0, 1.5 or 2.0 g/kg ethanol (chosen as training drug) and the opposite arm after administration of water. Only correct trials were rewarded. All the rats learned the discrimination task. Substitution tests with different doses of ethanol in all the three groups and with the non-competitive NMDA antagonist, dizocilpine (MK-801), in the 2.0 g/kg ethanol-trained group provided a pharmacological validation of the paradigm. Advantages and disadvantages of this procedure are discussed.

Animals