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Biomedical subjects

A Ambrosini

Publications and source records attributed to A Ambrosini.

At least 37 records · Page 2Linked to original sources

Neuromuscular transmission in migraine: a single-fiber EMG study in clinical subgroups.

OBJECTIVE: To search for impairment of neuromuscular transmission by single-fiber electromyography (SFEMG) in patients with common forms of migraine. BACKGROUND: P/Q Ca(2+) channels are genetically abnormal in most cases of familial hemiplegic migraine (International Headache Society [IHS] code 1.2.3) and may be involved in other types of migraine. Besides in the brain, these channels are found in motor nerve endings, where they control stimulation-induced acetylcholine release. If they are functionally abnormal, the neuromuscular transmission might be impaired. METHODS: Sixty-two migraineurs (18 without aura, IHS code 1.1; 19 with typical aura, IHS code 1.2.1; 10 with prolonged aura, IHS code 1.2.2; 15 with and without aura) and 16 healthy control subjects underwent stimulation SFEMG. Results were expressed as the mean value of consecutive differences (MCD) and percentage of single-fiber abnormalities (abnormal jitter or impulse blocking). RESULTS: Average MCD was comparable in control subjects and migraineurs (17.1 +/- 2.6 versus 17.5 +/- 4.7 microsec). By contrast, single-fiber abnormalities were found in 17 patients but in none of the control subjects (p = 0.036). Most of these patients had unilateral sensorimotor symptoms and/or aphasia and/or loss of balance during the aura. SFEMG abnormalities were significantly correlated with the occurrence of these clinical features and with a diagnosis of migraine with prolonged aura. CONCLUSIONS: Stimulation SFEMG shows mild abnormalities of neuromuscular transmission in a subgroup of migraineurs with aura, characterized by clinical features frequently found in human P/Q Ca(2+) channelopathies. These abnormalities might thus be due to genetically modified P/Q Ca(2+) channels.

Action Potentials↗

Laurdan fluorescence: a simple method to evaluate sperm plasma membrane alterations.

OBJECTIVE: To determine, by a simple fluorescence method, sperm plasma membrane alterations related with changes of lipid bilayer that, together with routine semen analysis, could help to elucidate the causes of the unexplained male infertility problems. DESIGN: Pilot study. SETTING: Andrology laboratory and biochemistry institute, medical school. PATIENT(S): Men whose semen was studied for infertility problems. INTERVENTIONS(S): No therapeutic intervention was performed on patients. MAIN OUTCOME MEASURE(S): Presence of spermatozoa plasma membrane alterations evidenced by evaluation of Laurdan fluorescence Generalized Polarization (GP) and reported as a function of increasing cell concentration, spermatozoa total motility, linear speed, and vitality. RESULT(S): Reporting GP values as a function of increasing sperm cell concentration, it is evident that the samples are distributed in two distinct areas: at >32 x 10(6) cells per milliliter, mean GP value was 0.303 +/- 0.015, whereas for lower sperm cell concentrations, the mean GP was 0.365 +/- 0.026 (P<.001). These data indicate that the spermatozoa plasma membranes are characterized by liquid-crystalline phases with different ordering degree and polarity and that about 50% of samples with normal semen characteristics (> or =20 x 10(6) cells per milliliter) show high GP values. CONCLUSION(S): Laurdan fluorescence can be used as a simple method to evaluate spermatozoa plasma membrane alterations, particularly in a group of infertile men presenting normal semen parameters. In these samples, Laurdan could be used as a simple tool for infertility assessment. In fact, it is known that compositional and physicochemical alterations of bilayer features can be important for the fertilizing ability of spermatozoa because they are necessary for a proper physiological membrane activity.

2-Naphthylamine↗

Neuromuscular transmission in migraine patients with prolonged aura.

P/Q Ca2+ channels are genetically abnormal in most cases of familial hemiplegic migraine (FHM) and may be involved in other types of migraine. They are also found at the neuromuscular junctions, where they control stimulation-induced acetylcholine release. Prolonged aura is a very frequent clinical feature in FHM patients. The objective of this study was thus to explore neuromuscular transmission in migraine with typical and prolonged aura patients. We performed single fiber electromyography (SFEMG) in such patients and compared them to a group of healthy volunteers. Results were expressed as mean jitter (MCD) and percentage of single endplate abnormalities. Mean MCD was on average comparable in controls and migraineurs. By contrast, single endplate abnormalities were only found in patients (p < 0.01), especially in those with prolonged aura (p < 0.001). These results suggest subtle impairment of neuromuscular transmission in a subgroup of migraineurs characterized by prolonged aura, which might be due to dysfunctioning P/Q Ca(2+)-channels.

Action Potentials↗

Steady-state and time resolved fluorescence of albumins interacting with N-oleylethanolamine, a component of the endogenous N-acylethanolamines.

The functions of N-acylethanolamines, minor constituents of mammalian cells, are poorly understood. It was suggested that NAEs might have some pharmacological actions and might serve as a cytoprotective response, whether mediated by physical interactions with membranes or enzymes or mediated by activation of cannabinoid receptors. Albumins are identified as the major transport proteins in blood plasma for many compounds including fatty acids, hormones, bilirubin, ions, and many drugs. Moreover, albumin has been used as a model protein in many areas, because of its multifunctional binding properties. Bovine (BSA) and human (HSA) serum albumin are similar in sequence and conformation, but differ for the number of tryptophan residues. This difference can be used to monitor unlike protein domains. Our data suggest that NOEA binds with high affinity to both albumins, modifying their conformational features. In both proteins, NOEA molecules are linked with higher affinity to hydrophobic sites near Trp-214 in HSA or Trp-212 in BSA. Moreover, fluorescence data support the hypothesis of the presence of other NOEA binding sites on BSA, likely affecting Trp-134 environment. The presence of similar binding sites is not measurable on HSA, because it lacks of the second Trp residue.

Circular Dichroism↗

Apoptosis induced by 2-chloro-adenosine and 2-chloro-2'-deoxy-adenosine in a human astrocytoma cell line: differential mechanisms and possible clinical relevance.

We have previously demonstrated that 2-chloro-adenosine (2-CA) can induce apoptosis of rat astroglial cells (Abbracchio et al. [1995] Biochem. Biophys. Res. Commun. 213:908-915). In the present study, we have characterized, for the first time, the effects induced on a human astrocytoma cell line (ADF cells) by both 2-CA and its related analog 2-chloro-2'-deoxy-adenosine (2-CdA, that is employed as anti-cancer agent in chronic lymphoid malignancies). Exposure of these cells to either adenosine analog resulted in time- and concentration-dependent apoptosis. Experiments with pharmacological agents known to interfere with adenosine receptors, its membrane transporter, and intracellular nucleoside kinases showed that: (i) cell death induced by either adenosine analog did not depend on extracellular adenosine receptors, but on a direct intracellular action; however, only in the case of 2-CA, was entry into cells mediated by the specific nitrobenzyl-tioinosine-sensitive transporter; (ii) for both adenosine analogs, induction of apoptosis required the phosphorylation/activation by specific intracellular nucleoside kinases, i.e., adenosine kinase for 2-CA, and deoxycytidine kinase for 2-CdA. In addition, only in the case of 2-CdA, was induction of apoptosis preceded by a block of cells at the G2/M phase of the cell cycle. Finally, at concentrations of either analog that killed about 80-90% of astrocytoma cells, a significantly lower effect on the viability of primary cortical neurons was observed. In conclusion, both adenosine analogs can trigger apoptosis of human astrocytoma cells, albeit with different mechanisms. This effect together with the relative sparing of neuronal cells, may have potential clinical implications for the therapy of tumors of glial origin.

2-Chloroadenosine↗

cAMP cascade leads to Ras activation in cortical neurons.

Monoaminergic G protein-coupled receptors (GPCRs) are highly expressed in the CNS at the cerebrocortical level, where they support a variety of behavioural responses. To elucidate possible intracellular signalling pathways coupled to these receptors, we have studied their ability to activate extracellular signal-regulated kinases (ERKs) in cultured cortical neurons. An increase in ERK activity was observed after stimulation of neurons with dopamine or serotonin, and with agonists selective for various GPCRs. In addition, ERK activation was also observed following treatment with phorbol dibutyrate (PdBu) and forskolin, activators of protein kinase C (PKC) and protein kinase A (PKA), respectively. Concomitant with ERK activation, all the monoaminergic agonists tested also increased the level of active Ras (Ras-GTP). Surprisingly, Ras activation was also observed after activation of cAMP pathway, and this effect was at least in part mediated by PKA. Ras activation by cAMP was unique for neurons, since in PC12 cells forskolin caused activation of ERK but did not increase Ras-GTP level. These results highlight the relevance of Ras as a target for multiple signalling cascades leading to activation of the ERK pathway in neurons.

Animals↗

Prophylactic treatment of migraine with beta-blockers and riboflavin: differential effects on the intensity dependence of auditory evoked cortical potentials.

OBJECTIVE: To investigate the influence of different pharmacological treatments on the intensity dependence of auditory evoked cortical potentials in migraineurs. BACKGROUND: Between attacks, patients with migraine show abnormalities in cortical information processing and decreased brain mitochondrial energy reserve. Both are most probably relevant for migraine pathogenesis, and they could be differentially modified by prophylactic drug therapy. Design.-The intensity dependence of the auditory evoked cortical potentials is, on average, increased in migraine. We have studied this intensity dependence in 26 patients before and after a 4-month period of prophylaxis with beta-blockers (n = 11, all migraine without aura; metoprolol or bisoprolol) or riboflavin (n = 15, migraine without aura: 13, migraine with aura: 2). Recordings were performed at least 3 days before or after an attack. RESULTS: After the treatment with beta-blockers, the intensity dependence of the auditory evoked cortical potentials was significantly decreased (before: 1.66+/-1.02 microV/10 dB; after: 0.79+/-1.06 microV/10 dB, P=.02). The decrease in intensity dependence was correlated significantly with clinical improvement (r = .69, P = .02). There was no change in intensity dependence after riboflavin treatment (before: 1.80+/-0.81 microV/10 dB; after: 1.56+/-0.83 microV/10 dB, P = .39), although the majority of patients showed improvement. CONCLUSIONS: These results confirm that beta-blockers and riboflavin act on two distinct pathophysiological mechanisms. Combining both treatments might enhance their efficacy without increasing central nervous system side effects.

Adrenergic beta-Antagonists↗

Influence of colors on habituation of visual evoked potentials in patients with migraine with aura and in healthy volunteers.

OBJECTIVE: To investigate whether colored glasses influence the habituation of visual evoked potentials. BACKGROUND: We have previously shown that during pattern-reversal stimulations lasting 2 minutes the amplitude of the visual evoked potential increases in migraine with and without aura between attacks, whereas it decreases in healthy volunteers. Red light was found to increase visually evoked EEG fast activity only in children with migraine with aura. Wearing rose-tinted glasses for 4 months decreased attack frequency in parallel with a reduction of the visually evoked EEG fast activity. METHODS: We compared the change in amplitude of the visual evoked potential using five different tinted glasses in 12 patients with migraine with aura and in 10 healthy volunteers. During continuous stimulation at 3.1 Hz, five blocks of 50 responses were sequentially averaged using red, yellow, green, blue, and grey glasses and without glasses in a random order and analyzed in terms of latencies and N1-P1 amplitudes. Amplitude changes were calculated for each block by comparison with the first block in every condition and analyzed statistically using Zerbe's method. RESULTS: In healthy volunteers, the visual evoked potential amplitude increased with red glasses compared to without glasses (P = .05) or with green glasses (P = .03). In patients with migraine with aura, no significant difference was detected using colored glasses. Our findings in healthy volunteers are in line with earlier reports of increased excitability of the human visual cortex when exposed to red light. The lack of such a pattern in patients with migraine with aura suggests that the visual cortex is interictally hypoexcitable rather than hyperexcitable, which is consistent with studies of transcranial magnetic stimulation.

Adult↗

Impairment of neuromuscular transmission in a subgroup of migraine patients.

Neuronal voltage-dependent P/Q Ca2+ channels are genetically abnormal in many cases of familial hemiplegic migraine and possibly associated with the more common forms of migraine with and without aura. Besides the brain, these channels are found in motor nerve endings where they control stimulation-induced acetylcholine release. Using single fiber EMG recordings we were able to demonstrate subclinical abnormalities of neuromuscular transmission in a subgroup of patients suffering from migraine with aura. This could be related to genetic abnormalities of P/Q Ca2+ channels in certain patients suffering from migraine with aura, which needs to be explored by proper genetic analyses.

Adult↗

"Gating" of human short-latency somatosensory evoked cortical responses during execution of movement. A high resolution electroencephalography study.

The present study aimed at investigating gating of median nerve somatosensory evoked cortical responses (SECRs), estimated during executed continuous complex ipsilateral and contralateral sequential finger movements. SECRs were modeled with an advanced high resolution electroencephalography technology that dramatically improved spatial details of the scalp recorded somatosensory evoked potentials. Integration with magnetic resonance brain images allowed us to localize different SECRs within cortical areas. The working hypothesis was that the gating effects were time varying and could differently influence SECRs. Maximum statistically significant (p<0. 01) time-varying gating (magnitude reduction) of the short-latency SECRs modeled in the contralateral primary motor and somatosensory and supplementary motor areas was computed during the executed ipsilateral movement. The gating effects were stronger on the modeled SECRs peaking 30-45 ms (N30-P30, N32, P45-N45) than 20-26 ms (P20-N20, P22, N26) post-stimulus. Furthermore, the modeled SECRs peaking 30 ms post-stimulus (N30-P30) were significantly increased in magnitude during the executed contralateral movement. These results may delineate a distributed cortical sensorimotor system responsible for the gating effects on SECRs. This system would be able to modulate activity of SECR generators, based on the integration of afferent somatosensory inputs from the stimulated nerve with outputs related to the movement execution.

Adult↗

The value of serum CA 125 and association CA 125/CA 19-9 in endometrial carcinoma.

One hundred and twelve women with endometrial carcinoma were studied with serum sampling to determine preoperative and postoperative levels of CEA, CA 15-3, CA 19-9, TPA and CA 125. After surgical treatment 88 patients had stage I, 8 stage II, 14 stage III and 2 stage IV disease. Before treatment the sensitivity of CEA, CA 15-3, CA 19-9, TPA and CA 125 was 22.3% (25/112), 32.1% (36/112), 22.3% (25/112), 45.5% (51/112), 33.9% (38/112), respectively. According to pathological stage a statistically significant difference between intrauterine (96 cases) and extrauterine disease (16 cases) was noted only for CA 125 (28.1% vs. 68.7%) and CA 15.3 (28.1% vs. 56.2%). In relation to histological grading CA 125 rises progressively from well-differentiated cases to poorly-differentiated tumors. During the follow-up the most reliable marker was CA 125: values more than 35 U/ml of this marker resulted positive in 50% of relapsed cases and only in 5.1% of disease-free cases, thus demonstrating a high specificity. The association of various markers during the follow-up allowed us to reveal interesting results only for the CA 125/CA 19-9 combination. In fact the combined use of these markers permitted a high sensitivity (83.3%), with only 12.8% false positive cases, so with a high specificity.

Adenocarcinoma↗

Immunohistochemical expression of BerEP4, a new epithelial antigen, in endometrial carcinoma: correlation with clinical parameters.

OBJECTIVE: To assess the immunochemical expression of BerEP4, a new epithelial antigen in endometrial carcinoma. METHODS: We studied 45 cases of endometrial carcinoma in which the BerEP4, CEA and TAG-72 antigens were searched by an immunohistochemical method. We evaluated the correlations among the immunohistochemical positivity and the grading, histotype, stage and receptorial status of the neoplasia. RESULTS: CEA was positive in 29 out of 45 cases (64.4%), TAG-72 in 17 out of 45 cases (37.7%) and BerEP4 in 31 out of 45 cases (68.9%). Both TAG-72 and CEA were inversely related to the grading while, with regard to the histotype, CEA resulted as highly positive in the 5 cases of adenoacanthoma. CONCLUSION: BerEP4 did not show any correlation with grading, histotype, stage of disease or receptorial status of the carcinoma.

Antigens, Neoplasm↗

[The rationalization of the follow-up of hormonal replacement treatment in menopause].

BACKGROUND: Decision making about the opportunity of starting or continuing hormone replacement therapy (HRT) in menopause should rely on an overall evaluation of its risks and benefits for the women's health; the evaluation of HRT cost-benefit ratio, however, should include its possible outcomes from an economical point of view. In this view, and with the certainty that menopausal patients should be protected by proper treatments, our case series has been evaluated in order to improve the quality of our clinical schedules for both their access to HRT and the treatment follow-up. METHODS: Two groups of patients have been considered the first one consisted of 560 women observed during '97 for climacteric symptoms and candicated to begin HRT. The second one consisted of 100 women on HRT for 1 to 6 years. In the first group we considered which test and with which frequency were responsible for stopping or delay the beginning of therapy; while in the second group we evaluated the reasons for stopping treatment. RESULTS AND CONCLUSIONS: On the basis of our experience, the exams required before starting HRT seem to be the following: patient history, mammography, densitometry and endometrial sample as well as the parameters of glucose lipidic, coagulative and hepatic metabolism. Densitometry is useful in the annual follow-up only in patients with bone alterations from the beginning. The same exams seem required for the follow-up, with the exception of bone densitometry which should be performed yearly only in patients with bone demineralization.

Climacteric↗

Nitrite and nitrate levels in cerebrospinal fluid of normal subjects.

In order to evaluate the involvement of nitric oxide in neurologic disorders it is important to generate controlled values of its metabolites nitrite and nitrate in human cerebrospinal fluid (CSF). Samples of CSF obtained from 14 patients without neurologic diseases were analysed for nitrite and nitrate concentration by reverse phase chromatography with ultraviolet (UV) detection. For comparison, the levels of nitrite in the same samples were also measured by reverse phase chromatography coupled with electrochemical detection and those of nitrate by ion chromatography coupled with UV detection. A good correlation was found for the concentration values of both ions obtained with the two procedures. Then, 10.41 +/- 0.47 ng/ml of nitrite and 2.92 +/- 0.37 ng/ml of nitrate could be regarded as reliable values in control subjects. No correlation between age and levels of nitrite and nitrate was observed.

Aged↗

Responses of human primary sensorimotor and supplementary motor areas to internally triggered unilateral and simultaneous bilateral one-digit movements. A high-resolution EEG study.

We modelled the responses of human primary sensorimotor areas and supplementary motor area to simple, self-initiated unilateral and simultaneous bilateral middle finger movements using a novel high-resolution electroencephalography technology. The results support the view that these cortical motor areas are involved in parallel and present similar activity in the preparation, initiation, and execution of the contralateral and bilateral movements. Furthermore, the left primary sensorimotor area (dominant hemisphere) appears to be activated more than the right primary sensorimotor area during the preparation and performance of the ipsilateral movements.

Adult↗

Human short latency cortical responses to somatosensory stimulation. A high resolution EEG study.

Human short-latency cortical responses to median nerve stimulation were investigated with a new high resolution electroencephalography technology that markedly enhanced spatial details of somatosensory-evoked potentials (SEPs). Maximum amplitude potentials were estimated over contralateral and/or frontal-mesial scalp regions about 20, 22, 24, 26, 30, 32 and 45 ms following the stimulation. Frontal-lateral P20-N24-N30-P45 and parietal-lateral N20-P24-P30-N45 showed dipolar patterns, whereas frontal-mesial N24-N30-P45 and central-lateral P22-N26-N32-P45 presented no clearcut dipole counterpart. Plausibly, the spatially enhanced frontal-parietal SEP components were generated (tangential dipoles) within the lateral central sulcus cortex, and anticipated the central-lateral and frontal-mesial components generated (radial dipoles) from the crown of the pre- and/or post-central gyri and the supplementary motor area, respectively.

Cerebral Cortex↗

Changes in nitric oxide metabolite levels in stimulated substantia nigra neurons.

Simultaneous quantification of the two major nitric oxide (NO) metabolites, nitrite and nitrate, was performed on mouse mesencephalic neurons in vitro, in basal conditions or after excitatory stimuli. Measurements were made using both extracellular medium and cytosolic extracts. Basal metabolite levels were stable up to 5 min. Depolarization by high levels of potassium promptly increased extracellular nitrite (270% of basal, peak at 10s) leaving intracellular levels unchanged. Glutamate receptor agonists caused a rapid increase in intracellular, but not extracellular, nitrite levels (240% of basal, peak at 30s). Intracellular nitrate levels raised slowly after addition of potassium (215% of basal at 1 min) or N-methyl-D-aspartate (230% of basal at 5 min), but not after quisqualate. The different dynamic variations of the two NO metabolites point to the specificity of the activated metabolism according to the type of excitatory stimulus.

Animals↗