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Biomedical subjects

F Melis

Publications and source records attributed to F Melis.

At least 19 recordsLinked to original sources

Poor reliability of heart rate monitoring to assess oxygen uptake during field training.

The aim of this study was to quantify the error associated with the assessment of oxygen uptake (VO2) by heart rate (HR) monitoring in 15 athletes freely performing their training session. A laboratory-derived equation was used on the running track to calculate VO2 (VO2est) from HR. Oxygen uptake was also assessed by means of a portable gas analyzer (VO2real). Bland and Altman statistics were carried out in order to evaluate agreement between VO2real and VO2est. The excess in carbon dioxide production (CO2excess) was measured to test the hypothesis that the subject with the highest CO2excess had the highest VO2est - VO2real difference. VO 2real was on average 0.14 l x min (-1) below VO2est. The limits of agreement of this difference were between + 0.77 and - 0.48 l x min (-1). Thus, on average VO2real was overestimated by VO2est. Spearman non-parametric statistics found a significant correlation between CO2excess and VO2est - VO2real difference (R = 0.55, p = 0.031). This study demonstrates that the use of HR monitoring to assess VO2 during field training overestimates VO2real, especially when a substantial increase in CO2excess occurs. Therefore, this method should be used with care when an excessive amount of CO2 is produced as occurs in activities that involve the lactic acid anaerobic source of energy production.

Adult↗

Persistent neutralizing antibodies abolish the interferon beta bioavailability in MS patients.

BACKGROUND: MxA is an antiviral protein exclusively induced by type I interferons (IFN) and some viruses, and MxA gene expression is one of the most appropriate markers for measuring the biologic activity of exogenous IFNbeta. METHODS: A new quantitative-competitive PCR method was used to quantify MxA mRNA in peripheral blood mononuclear cells of 99 treatment-naïve and 92 IFNbeta-treated patients with MS (22 Avonex, 17 Betaferon, and 53 Rebif-22). Every 3 months, IFNbeta-induced neutralizing antibodies (NAb) were evaluated in sera using a cytopathic effect assay. Three categories of patients were identified: NAb negative (NAb-), persistent NAb positive (NAb+, >or=2 consecutive positive samples), and isolated NAb+ (one positive sample). RESULTS: Treatment-naïve patients expressed detectable MxA mRNA levels (mean = 36 +/- 32 fg MxA/pg glyceraldehyde-3-phosphate dehydrogenase (GAPDH); range 1 to 160) and an upper normal threshold was established (mean + 3 SD = 132 fg MxA/pg GAPDH). IFNbeta-treated patients exhibited more than 11-fold higher levels (mean = 412 +/- 282 fg MxA/pg GAPDH; range 16 to 1,172). However, 17 patients did not exhibit an increase in MxA mRNA level; 15 of these 17 patients showed a concurrent Nab+ titer. Moreover, 13 were persistent NAb+. Isolated NAb+ patients did not show a decrease in bioavailability of IFNbeta (n = 9; mean = 567 +/- 366 fg MxA/pg GAPDH; range 83 to 1,120). In NAb- patients, bioavailability was comparable among the three different IFNbeta preparations 12 hours after injection. CONCLUSION: During IFNbeta therapy, the presence of NAb reduced or abolished bioavailability in a relevant percentage of patients. These data could be important for the early detection of patients with MS who are not responsive to IFNbeta therapy.

Antibodies↗

Does reduction of blood prolactin levels reveal the activation of central dopaminergic pathways conveying reward in top athletes?

Prolactin blood levels are modulated directly by CNS via the known tubero-infundibular dopaminergic neurons which exert an inhibitory action on lactotrope cells in the hypophysis. Prolactin is devoid of peripheral negative feedback and via lesser known central pathways (e.g., mesolimbic and mesocortical) might be further tuned by means of appropriate stimuli (e.g., addictive drugs, gambling, exercise and so forth). Therefore, a prolactin test can be utilised to obtain an objective index to assess the compliance to exercise in men. This index may be used to identify the most suitable athlete for a given sport and mainly to survey exercise as rewarding behaviour in trained people. Prolactin was assessed in male top world windsurfers (WS) and in a control group of non-windsurfer trained subjects (CS) during an exercise simulating marine windsurfing. The result was that prolactin levels decreased significantly in WS with respect to CS when compared with pre-test levels (WS: -22.7%; P<0.05).

Dopamine↗

Haemodynamics during a complete exercise induced atrioventricular block.

The case is reported of an athlete who, during an exercise test, had a complete atrioventricular block without symptoms of cardiac output failure. Heart rate, stroke index, cardiac index, and myocardial contractility were monitored during the episode by an impedance cardiograph. The most important findings of this report are the continuous increase in stroke index, which compensated for the lack of heart rate response, and the normal cardiac index values achieved during the exercise. This stroke index response was mainly due to an increase in myocardial contractility.

Adult↗

Differential effects of three interferon betas on neutralising antibodies in patients with multiple sclerosis: a follow up study in an independent laboratory.

OBJECTIVE: To evaluate the incidence and the prevalence of neutralising antibodies (NABs) to three interferon beta (IFNbeta) products in patients with multiple sclerosis (MS). METHODS: Sera were tested from 125 patients with relapsing-remitting MS. Patients were treated with IFNbeta-1b (Betaferon, n = 29) 8 MIU subcutaneously every other day, IFNbeta-1a (Avonex, n = 44) 30 microg intramuscularly once weekly, or IFNbeta-1a (Rebif, n = 36) 22 microg subcutaneously three times weekly for 6 to 18 months. An additional 16 patients were treated with Rebif 22 microg intramuscularly once or twice weekly. NABs were assessed using the cytopathic effect assay before treatment and every three months during treatment. Patients with two or more consecutive positive samples were considered to be persistent NAB positive (NAB+). RESULTS: At baseline, no patients were NAB+. NABs developed during the first three months of treatment and continued to develop until month 18. Over 18 months of treatment, the risk of being persistent NAB+ was 31% for Betaferon, 15% for Rebif, and 2% for Avonex (Betaferon versus Avonex, p = 0.001; Betaferon versus Rebif, p = 0.19; Rebif versus Avonex, p = 0.04). In all patients with one or more NAB+ samples, the risk of becoming NAB+ was 38% for Betaferon, 18% for Rebif, and 7% for Avonex (Betaferon versus Avonex, p = 0.0007; Betaferon versus Rebif, p = 0.10; Rebif versus Avonex, p = 0.07). At month 18, the prevalence of persistent NAB+ patients was 31.6% for Betaferon, 18.7% for Rebif, and 4% for Avonex. Numbers of NAB+ patients observed were similar with intramuscular Rebif and with subcutaneous Rebif. CONCLUSION: The three IFNbeta preparations have different degrees of immunogenicity, with Betaferon producing the highest incidence of NABs and Avonex the lowest. These differences should be considered by neurologists when selecting treatment for their patients with MS because NABs can reduce both bioavailability and clinical efficacy of IFNbeta.

Adult↗

External mechanical work versus oxidative energy consumption ratio during a basketball field test.

BACKGROUND: A field test consisting of 5 continuous runs at the maximum speed possible, playing the ball, starting from the centre line to the basket with a final shot, was studied in order to obtain an index of mechanical work efficiency in basketball players (micro-index=Jmec/Joxy) and evaluate the correlation between micro-index and velocity, acceleration, mechanical power and lactacid anaerobic capacity, respectively. METHODS: Eight male basketball players were studied; Jmec was the external mechanical work output obtained by means of a video image analysis software which gave the potential and the kinetic translational energies of athletes running and jumping and their velocity, acceleration and mechanical power. By means of a telemetric device (Kosmed K4), for measuring O2 consumption ( VO2), we obtained oxidative work (Joxy). By using this device we also assessed the excess of CO2, which was considered an index of lactacid anaerobic capacity. RESULTS: Non-parametric Spearman statistics revealed a significant correlation between mu index and mean velocity (p<0.01, r=0.90), acceleration (p<0.05, r=0.78), mechanical power (p<0.05 r=0.76) and CO2 excess (p<0.01, r=0.95). Consequently athletes who had the best index of mechanical efficiency also had the best biomechanical quality and the greatest lactacid anaerobic capacity. CONCLUSIONS: This study strongly supports the hypothesis that in basketball anaerobic capacity is important in achieving high values of speed, acceleration, mechanical power and endurance velocity.

Acceleration↗

Evaluation of bioavailability of three types of IFNbeta in multiple sclerosis patients by a new quantitative-competitive-PCR method for MxA quantification.

Intracellular expression of human myxovirus protein A (MxA) is exclusively induced by type I IFNs (IFNalpha,beta,omega) or by some viruses and it is strongly increased under IFN treatment. We set up an internally controlled quantitative-competitive polymerase chain reaction (qc-PCR) that quantifies MxA mRNA expressed in human peripheral blood mononuclear cells (PBMC). Our qc-PCR is accurate because the mean ratio of copy number estimated by qc-PCR to that quantified spectrophotometrically is 1.08+/-0.03, moreover it is repeatable with high sensitivity (1 fg MxA/pg GAPDH). MxA mRNA was tested in 47 Relapsing-Remitting Multiple Sclerosis (RR-MS) untreated patients and in 48 patients treated with one of the 3 IFNbeta licensed for MS (24 with Rebif, 14 with Avonex and 10 with Betaferon). All the 48 treated patients were negative to IFNbeta neutralising antibodies (NABs) as tested in our laboratory using a cytopathic assay (CPE). MxA mRNA levels were detectable in all untreated patients (mean 24+/-18 fg MxA/pg GAPDH) and significantly higher levels were found in all the treated patients 12 h after IFNbeta administration (mean 499+/-325 fg MxA/pg GAPDH); furthermore, the three types of IFNbeta showed comparable bioavailability. Our data indicate that the bioavailability of the three available types of IFNbeta can be evaluated by MxA qc-PCR.

GTP-Binding Proteins↗

Frequency-dependent LTP/LTD in guinea pig Deiters' nucleus.

Synaptic plasticity was studied in the lateral vestibular nuclei (LVN) of the guinea pig in vivo. High frequency stimulation (HFS) of increasing or decreasing frequencies was applied to the ipsilateral vestibular nerve. Vestibular field potentials (VFPs) and extracellular single unit activity evoked in the LVN by electrical stimulation of the ipsilateral vestibular nerve, were analyzed before and after the application of different protocols of HFS. Results show that the monosynaptic component of the VFPs undergo long-term potentiation (LTP) with stimulation of 100 Hz applied for 20 s lower frequencies, applied for shorter periods, induce only a transient post-tetanic potentiation. This potentiation, although long lasting, is not permanent since it is susceptible of a reversal or cancellation by opposite patterns of HFS that determine a depression or depotentiation of the previously acquired potentiation. The results demonstrate that the plasticity phenomena that take place at the level of the LVN neurons are not steady but undergo continuous adjustment of their sign and gain depending on the variable flow of vestibular information that reach the nuclei from the labyrinthine receptors.

Animals↗

Neurotoxic effect of lead at low concentrations.

The effects of lead exposure at low concentrations were evaluated by studying the post-rotatory nystagmus (PRN) in two groups of rats exposed for 3 months to 50 parts per million (ppm) of sodium acetate and 50 ppm of lead acetate, respectively, in the drinking water. Only animals treated with lead acetate showed changes of the PRN parameters which were significantly related to the concentration of lead in the blood and in brain structures. The patterns of PRN responses were characterized and classified into four types: progressively inhibitory (40%), prematurely inhibitory (25%), late inhibitory (25%), and excitatory-inhibitory (10%). No alterations of the PRN parameters were observed in the animals treated with sodium acetate. The results show that exposure to lead, even at low concentrations, impairs both sensory and motor functions. The findings also point out that the vestibular system and brain stem structures which generate and control the PRN represent targets of the action of this heavy metal. Finally, the results indicate that the evaluation of the vestibulo-ocular-reflex can provide a test suited for the screening of the neurotoxic effects of lead even in the absence of clinical signs typical of lead intoxication.

Animals↗

Autonomic nervous system activity and life threatening arrhythmias in experimental epilepsy.

In the present study the possible derangement of the autonomic system and its influence in life threatening arrhythmias were analysed during paroxysmal activity. In hemispherectomized rats a paroxysmal activation of the hypothalamic and mesencephalic cardioarrhythmogenic triggers was performed by topical application of penicillin-G. Blood gas parameters and electrical activity of the thalamus, hypothalamus, vagal nerve fibre, ECG and arterial blood pressure were simultaneously monitored in basal conditions and repeated after the appearance of paroxysmal activity. Temporal correlation analysis was carried out. Results showed that during activation of these triggers, the spontaneous vagal nerve fibre activity significantly increased and triggered the appearance of cardiac arrhythmias which could become life threatening and induce animal death when blood gas and electrolytic parameters were simultaneously impaired. These experiments suggest that fatal evolution of the heart impairment is related not only to an autonomic cardiac trigger, but also to a concomitant metabolic derangement, which most likely shares the same autonomic origin.

Animals↗

Hemodynamic during a postexertional asystolia in a healthy athlete: a case study.

Hemodynamic events leading to spontaneous postexertional vasovagal syncope are not completely understood because of the lack of beat-to-beat data. We report a case study of a young athlete who undergoes a syncopal episode during the recovery period following a maximal cycle-ergometer test. The episode was monitored by an impedance cardiograph which can gather noninvasively beat-to-beat the flow of heart rate (HR), stroke volume (SV), cardiac output (CO), diastolic filling rate (SV/DT), and myocardial contractility index (PEP/LVET). The most important findings of this report are the dramatic reduction of SV/DT preceding the syncope, the increment of SV together with the reduction of HR preceding and following the syncope, the prompt recovery of CO values after the syncopal episode despite the bradycardia, and the reduction of PEP/LVET after the syncope. This report confirms the importance of active recovery immediately after strenuous exercise and supports the hypothesis that the reduction of SV/DT in the presence of an inotropic stimulation can trigger the vasovagal reaction.

Adolescent↗

Epileptic discharge of cortical, subcortical and spinal neurons in penicillin induced experimental epilepsy.

The sensitivity and electrophysiological patterns of paroxysmal activity induced in different brain structures by topical application of penicillin-G were evaluated in the rat. Recordings were carried out in five groups of animals, in telencephalon, diencephalon, mesencephalon, rombencephalon and spinal cords. The following analysis were carried out: frequency distribution histograms, latency and time course duration of paroxysmal activity, duration and amplitude of epileptic bursts. The results obtained showed that the nervous structures tested with penicillin-G had a different epileptogenic sensitivity and response pattern which significantly changed along the cerebral cortex-spinal cord axis. The highest epileptic sensitivity was observed in somatosensory cortex (SI) at 500-600 microns depth; in the other cortical layers, a significant lenghtening in latency was observed. Among the other structures, the spinal cord seemed to be the most sensitive target to the epileptogenic action of penicillin-G, whereas in the remaining structures, sensitivity significantly decreased in rostro-caudal direction. As far as the features of the paroxysmal activity are concerned, significant differences among tested structures were observed. In particular, within the SI cortex, the main differences were represented by the gradual increase in burst frequency and voltage from the surface to the IVth layer and by their subsequent decrease in deeper layers (V-VI). In the diencephalon, the paroxysmal activity was similar to that observed in more superficial and deeper cortical layers even though epileptic bursts showed a lower amplitude. Mesencephalon and rombencephalon displayed a paroxysmal activity with a distinctive feature, characterized by long lasting bursts of low amplitude, although bulbar outbursts showed a shorter duration than the mesencephalic ones. In the spinal cord, the epileptiform activity displayed a different paroxysmal pattern, characterized by the longest duration and the highest amplitude. The different sensitivities of the investigated brain structures to penicillin-G and the characteristics of the induced paroxysmal activity have been extensively discussed.

Animals↗

Field test for mechanical efficiency evaluation in matching volleyball players.

Field tests were performed in 10 volleyball (VB) players (4 females and 6 males) in order to obtain an index of mechanical work efficiency (mu' = Wmec/Woxy) while athletes played a game. Wmec was the mechanical work output, obtained by means of home made video image analysis software, by summing potential, kinetic translational and kinetic rotational energies of running and jumping athletes. Woxy was the oxidative energy consumption obtained from O2 consumption (VO2) by a telemetry device (Cosmed K2) that also gave values of pulmonary ventilation (VE) and heart rate (HR). VB were studied at rest before a game (R), during attacking phases (A) and during defensive phases (D). At R were found: VE = 11 +/- 1 l x min(-1), HR = 78 +/- 7b x min(-1), VO2 = 3.71 +/- 1.1 ml x kg(-1) x min(-1), Woxy = 75.1 +/- 22.3 J x kg(-1) x min(-1). During A all variables increased: VE = 49 +/- 6l x min(-1), HR = 149 +/- 15 b x min(-1), VO2 = 23.1 +/- 3.3ml x kg(-1) x min(-1), Woxy = 482.8 +/- 69.0 J x kg(-1) x min(-1), and Wmec 275.5 +/- 57.0 J x kg(-1) x min(-1) with mu'=0.57 +/- 0.09. In D HR (-9%), VE, VO2 and Woxy (-18%) were reduced when compared to A, decreasing mu' to 0.21 +/- 0.05. On the other hand mu' was found higher than 0.25 during A indicating an anaerobic contribution to energy expenditure; in D the mu' lower than 0.25 indicated a restoration of anaerobic energy sources. It might be proposed that a greater difference in mu' values between A and D also means a higher anaerobic energy contribution to the volleyball game.

Adult↗

The decrease of serotonin release induced by a tryptophan-free amino acid diet does not affect spatial and passive avoidance learning.

We assessed whether consumption of a diet lacking in tryptophan (TRP) resulted in alteration in learning and memory performance and hippocampal 5-HT release in rats. Two hours after the acute administration of TRP-free (T) and balanced (B) diet rats were trained in a one-trial passive avoidance task. The two groups of rats showed no significant difference in retention latencies. Two other groups of rats, fed with the above diets during the acquisition of a radial-arm maze task, showed no difference in baseline performance. The acute ingestion of the T diet produced a significant and long lasting decrease of hippocampal and cortical 5-HT release in rats when compared to the B diet, while the 12th day of the T diet, 5-HT was not detectable in the dialysate. These data indicate that the diminished brain release of 5-HT induced by a T diet is not sufficient to impair cognitive processes.

Animals↗

Acute administration of a tryptophan-free amino acid mixture decreases 5-HT release in rat hippocampus in vivo.

The effect of oral administration of a tryptophan-free amino acid mixture or the same mixture containing tryptophan (Trp) on hippocampal serotonin (5-HT) extracellular levels was studied using in vivo brain microdialysis of freely moving rats. During chloral hydrate anesthesia rats were implanted with dialysis probes in the dorsal hippocampus, and experiments were performed 24 h later. In vehicle-treated rats, the extracellular levels of 5-hydroxyindolacetic acid (5-HIAA) and 5-HT did not change during 240 min after ingestion. Oral administration of the Trp-free amino acid mixture significantly decreased basal 5-HT and 5-HIAA output 100 min after ingestion (65 and 81% of basal value, respectively) and remained at this level for another 140 min. The amino acid mixture containing Trp failed to significantly change basal extracellular levels of 5-HT, but enhanced that of 5-HIAA by approximately 134%. Moreover, in rats receiving the Trp-free amino acid mixture, the increase of hippocampal 5-HT release induced by d-fenfluramine (206%) was smaller than that released by the same drug in rats receiving the nutritionally balanced amino acid mixture (271%). Thus these results show that removal of Trp from the balanced amino acid mixture decreases spontaneous and d-fenfluramine-induced release of 5-HT in the hippocampus. In conclusion, our study supports the hypothesis that the mood-lowering effect observed in man after ingestion of a Trp-free amino acid mixture is associated with diminished 5-HT release in the brain.

Administration, Oral↗

Does long-term potentiation occur in guinea-pig Deiters' nucleus?

Long-term potentiation (LTP) was studied in the lateral vestibular nucleus (LVN-Deiters' nucleus) in guinea-pigs in vivo. Field potentials and extracellular single unit discharges were recorded in the LVN following electrical stimulation of the ipsilateral VIIIth nerve. High-frequency stimulation (HFS) of the VIIIth nerve fibres produced LTP of the monosynaptic component of the vestibular field potential. The LTP of the field potentials was paralleled by an increase of the evoked spike activity. Intranuclear administration of the NMDA antagonist MK-801 prevented LTP of the monosynaptic component of the vestibular field potentials and significantly suppressed the spontaneous firing of lateral vestibular neurones in a dose-dependent fashion. These results demonstrate that synapses between primary afferent fibres and second order LVN neurones undergo long lasting changes following HFS of the ipsilateral vestibular nerve.

Animals↗

Increased hippocampal acetylcholine release during a working memory task.

In this study we examined whether the food-reinforced alternation performance was associated with increased acetylcholine output in the dorsal hippocampus. Rats were trained to acquire the task using a T-maze. The control group consisted of rats introduced into the T-maze to run only on the day of dialysis. Acetylcholine release increased significantly in control rats only in the first 10 min after they were put into the T-maze. In trained rats acetylcholine output increased in the waiting cage as well as during trials in the T-maze. The increase in acetylcholine output in rats that had learned the task was significantly greater than in control rats.

Acetylcholine↗

Long-lasting changes of neuronal activity in the motor cortex of cats.

The effect of tetanic intracortical microstimulation (ICMS) of superficial layers of the motor cortex on unit discharges responding to stimulation of the peripheral receptive fields was examined in the motor cortex (area 4y). Single or multiple unit discharges were isolated from 15 recording sites near the stimulating electrodes. Following tetanic ICMS, the response to the same peripheral stimulation showed a long lasting increase at six recording sites, a long lasting decrease at two sites and transient increase or decrease at four sites. In the rest of the sites, tetanic ICMS had no effect. The results demonstrate the existence of use-dependent modification of information processing in the motor cortex and support the hypothesis that the motor cortex participates in learning motor skills.

Animals↗