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Biomedical subjects

E Martignoni

Publications and source records attributed to E Martignoni.

At least 37 records · Page 2Linked to original sources
PubMed1999

Determination of hydroxyl free radical formation in human platelets using high-performance liquid chromatography with electrochemical detection.

The formation of the hydroxyl free radical (HFR) can be quantified indirectly, by measuring two products of the hydroxylation of salicylic acid, 2,3-dihydroxybenzoate (2,3-DHB) and 2,5-dihydroxybenzoate (2,5-DHB). In this study, we used reversed-phase high-performance liquid chromatography with electrochemical (coulometric) detection to measure 2,3-and 2,5-DHB levels in human platelets. The limits of detection of the method were 10 and 5 fmol on column for 2,3-DHB and 2,5-DHB, respectively. We tested the technique by measuring increases in dihydroxybenzoate levels after exposure of platelets to experimentally induced oxidative stress. Then, we measured platelet levels of 2,3- and 2,5-DHB in patients with Parkinson's disease, under therapy with L-DOPA, and in normal subjects. We also measured platelet concentrations of L-DOPA and its major metabolite, 3-O-methyldopa (3-OMD). Parkinsonian patients showed increased levels of both 2,3- and 2,5-DHB. Platelet levels of 2,3-DHB were positively correlated with platelet levels of L-DOPA and 3-OMD. The technique we describe proved simple and extremely sensitive and may represent a useful tool for the study of oxidative stress in humans.

Adult↗
PubMed1999

Peripheral markers of oxidative stress in Parkinson's disease. The role of L-DOPA.

Oxidative stress plays a central role in the pathogenesis of Parkinson's disease (PD). L-DOPA, the gold standard in PD therapy, may paradoxically contribute to the progression of the disease because of its pro-oxidant properties. The issue, however, is controversial. In this study, we evaluated peripheral markers of oxidative stress in normal subjects, untreated PD patients and PD patients treated only with L-DOPA. We also measured platelet and plasma levels of L-DOPA, 3-O-methyldopa (the long-lasting metabolite of the drug), and dopamine. We found that isolated platelets of treated PD patients form higher amounts of 2,3-dihydroxybenzoate, an index of hydroxyl radical generation, than platelets of controls or untreated patients. In treated patients, platelet levels of 2,3-dihydroxybenzoate were positively correlated with platelet levels of L-DOPA, 3-O-methyldopa, and with the score of disease severity. Disease severity was correlated with platelet and plasma levels of L-DOPA, as well as with the daily intake of the drug. No significant differences in platelet levels of cytosolic and mitochondrial isoforms of the antioxidant enzyme superoxide dismutase were found between PD patients, either treated or untreated, and controls. Our findings lend further support to the hypothesis that L-DOPA might promote free radical formation in PD patients.

Antiparkinson Agents↗
PubMed1999

Modifications of local cerebral metabolic rates for glucose and motor behavior in rats with unilateral lesion of the subthalamic nucleus.

Inactivation of the subthalamic nucleus (STN) has attracted interest as a therapeutic tool in Parkinson's disease. The functional consequences of the inactivation, however, are uncertain. In this study definition of the pattern of changes of cerebral functional activity associated with lesion of the STN and dopaminergic stimulation, by using the [14C]deoxyglucose method, was sought. Six or 7 days following unilateral lesion of the STN, the animals were divided into two groups: One group (n = 10) was administered apomorphine (1 mg/kg) subcutaneously; the second group (n = 10) received saline. The [14C]deoxyglucose procedure was initiated 10 minutes following the drug or saline injection. The results show that systemic administration of apomorphine to rats with unilateral lesion of the STN causes ipsiversive rotational behavior and asymmetries of glucose utilization of defined brain areas, including the substantia nigra reticulata, globus pallidus, and entopeduncular nucleus. These nuclei are the main targets of the subthalamic excitatory projections. Lesion of the nucleus per se (without challenge with apomorphine) has no significant consequences on glucose utilization. The findings indicate that the STN is involved in the activation of the basal ganglia output nuclei induced by systemic dopaminergic stimulation.

Animals↗
PubMed1998

Hydroxyl radical production in the substantia nigra after 6-hydroxydopamine and hypoxia-reoxygenation.

To study the involvement of oxidative stress in 6-OHDA neurotoxicity, we investigated the production of the hydroxyl free radical (OH.) in the substantia nigra (SN) and the striatum (CS) several moments after intranigral injection of the neurotoxin, with or without an added episode of hypoxia (30 min, 95% N2, 5% O2). We utilized the hydroxylation of salicylate to 2,3 dihydroxybenzoic acid (2,3 DHBA) as indication of OH. production. When 2.3 DHBA levels were not modified, the levels of 2,5 DHBA were taken as an indication of cytochrome P450 (CYP 450) metabolism. 6-OHDA alone did not increase the production of 2,3 DHBA in the SN. 2,5 DHBA increased significantly after 120 min and was high up to 24 h. An episode of hypoxia (60 min after 6-OHDA injection) significantly worsened the decrease of dopamine (DA) in the striatum assessed 8 days after injection of 6-OHDA in the SN. Hypoxia performed 60 min and 24 h before or 24 h after 6-OHDA did not show any additional effect on striatal DA levels. Contrary to results obtained after 6-OHDA alone, 2,3 DHBA increased significantly 120 min after the injection, when the hypoxia-reoxygenation was added to the 6-OHDA treatment. Our data are showing a relationship between the increase in OH. production and a concomitant worsening of neuronal degeneration. As a whole, the results support the idea that neurons undergoing 6-OHDA neurotoxicity have their antioxidant defences affected and that oxidative stress is actually an important eliciting factor in 6-OHDA dependant neurodegeneration. However, OH. may not be the main radical species involved in this process. Additionally, 6-OHDA also appeared to provoke a long-term increase in CYP 450 activity.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1998

Cardiovascular autonomic modulation and activity of carotid baroreceptors at altitude.

1. To assess the effects of acute exposure to high altitude on baroreceptor function in man we evaluated the effects of baroreceptor activation on R-R interval and blood pressure control at high altitude. We measured the low-frequency (LF) and high-frequency (HF) components in R-R, non-invasive blood pressure and skin blood flow, and the effect of baroreceptor modulation by 0. 1-Hz sinusoidal neck suction. Ten healthy sea-level natives and three high-altitude native, long-term sea-level residents were evaluated at sea level, upon arrival at 4970 m and 1 week later.2. Compared with sea level, acute high altitude decreased R-R and increased blood pressure in all subjects [sea-level natives: R-R from 1002+/-45 to 775+/-57 ms, systolic blood pressure from 130+/-3 to 150+/-8 mmHg; high-altitude natives: R-R from 809+/-116 to 749+/-47 ms, systolic blood pressure from 110+/-12 to 125+/-11 mmHg (P<0.05 for all)]. One week later systolic blood pressure was similar to values at sea level in all subjects, whereas R-R remained elevated in sea-level natives. The low-frequency power in R-R and systolic blood pressure increased in sea-level natives [R-R-LF from 47+/-8 to 65+/-10% (P<0.05), systolic blood pressure-LF from 1.7+/-0. 3 to 2.6+/-0.4 ln-mmHg2 (P<0.05)], but not in high-altitude natives (R-R-LF from 32+/-13 to 38+/-19%, systolic blood pressure-LF from 1. 9+/-0.5 to 1.7+/-0.8 ln-mmHg2). The R-R-HF decreased in sea-level natives but not in high-altitude natives, and no changes occurred in systolic blood pressure-HF. These changes remained evident 1 week later. Skin blood flow variability and its spectral components decreased markedly at high altitude in sea-level natives but showed no changes in high-altitude natives. Neck suction significantly increased the R-R- and systolic blood pressure-LF in all subjects at both sea level and high altitude.3. High altitude induces sympathetic activation in sea-level natives which is partially counteracted by active baroreflex. Despite long-term acclimatization at sea level, high-altitude natives also maintain active baroreflex at high altitude but with lower sympathetic activation, indicating a persisting high-altitude adaptation which may be genetic or due to baroreflex activity not completely lost by at least 1 year's sea-level residence.

Adult↗
PubMed1997

Simultaneous determination of L-dopa and 3-O-methyldopa in human platelets and plasma using high-performance liquid chromatography with electrochemical detection.

Various high-performance liquid chromatographic (HPLC) methods for the determination of plasma levels of L-dopa and of its metabolite, 3-O-methyldopa (3-OMD), have been previously described. In this study, we report a modification of these methods, that enables the assay of these two compounds in platelets and plasma obtained from the same sample of whole blood. Reversed-phase (RP) HPLC with electrochemical (coulometric) detection was used. The within-run and between-run coefficients of variations, for the two compounds, were less than 10%, in both platelets and plasma; the detection limits for platelet levels of L-dopa and 3-OMD were 2 and 6 ng/10(9) platelets, respectively. In plasma, the detection limits for L-dopa and 3-OMD were 1 and 3 ng/ml, respectively. The method is rapid and simple. When applied to a population of patients with Parkinson's disease under treatment with L-dopa, this method revealed detectable levels of L-dopa and 3-OMD in the platelets of all patients. The application of this technique may provide new insights into the pharmacokinetics of L-dopa in patients with Parkinson's disease.

Adult↗
PubMed1997

Stimulation of corticotrophin-releasing hormone release by the obese (ob) gene product, leptin, from hypothalamic explants.

Recent data have suggested that adipocytes synthesize and secrete a 16 kDa peptide which acts centrally to regulate weight gain by suppressing appetite and activating the sympathetic nervous system. To exert such effects, it may function as an endogenous ligand in the CNS, since specific receptors (OB-R) have been recently reported to be widely distributed in the brain. We have speculated that this peptide, now known as leptin, may act centrally by stimulating the release of corticotrophin-releasing hormone (CRH), a recognized potent inhibitory modulator of appetite. We tested in vitro the effect of murine leptin on CRH secretion in the dose range of 0.1 pM-100 nM. The static rat hypothalamic incubation system used involved fresh hypothalamic explants maintained in EBSS with consecutive 20 min incubations, and estimation of CRH concentrations in the medium by a specific and sensitive radioimmunoassay. The effect of heat-denatured leptin at a dose of 1 nM and 10 nM, was also investigated. Any possible modulation of leptin effects by adrenergic pathways was then explored by coincubating hypothalami with leptin 10 nM and equimolar concentrations of the alpha 1-adrenergic antagonist prazosin or the beta-adrenergic antagonist propranolol. The active leptin, but not the heat-inactivated peptide, caused a dose-dependent stimulation of CRH release in vitro (p < 0.05- < 0.0001 vs control), with a plateau effect at a dose of 10 nM. The addition of either prazosin or propranolol was without effect on leptin-dependent CRH stimulation. These findings are consistent with the reported presence of leptin receptors in the rat brain, and suggest that leptin may act to regulate appetite at least in part by directly modulating the secretion of CRH from the hypothalamus. It would also appear that such effect occurs via a non-adrenergic mechanism.

Analysis of Variance↗
PubMed1997

Is seborrhea a sign of autonomic impairment in Parkinson's disease?

An increase of sebum excretion rate (SER) is frequently observed in patients suffering from Parkinson's disease (PD). Some authors attribute it to the hyperactivity of the parasympathetic system, while others consider the possible action of androgens or of MSH-hormone. The aim of our study was to verify and quantify SER in 70 parkinsonian patients and compare it with SER in 60 normal subjects. We found higher values of SER in male subjects, both in normal and in parkinsonian patients. The highest rate of excretion was observed in parkinsonian males, in agreement with the possible main role of androgens or testosterone in sebum excretion, while the phenomenon did not appear to be related to abnormalities of the autonomic nervous system. The association of PD and sex hormones might therefore be crucial for the developing of seborrhea.

Aged↗
PubMed1997

Premenstrual dysphoric disorder and eating disorders.

UNLABELLED: Premenstrual Dysphoric Disorder (PMDD) can be differentiated from Premenstrual Syndrome (PMS) by the use of the research criteria provided by the Diagnostic and Statistical Manual (DSM) IV. Indeed, PMS corresponds to mild clinical symptoms, such as breast tenderness, bloating, headache and concomitant minor mood changes, while premenstrual magnification occurs when physical and psychological symptoms of a concurrent axis I disorder get worse during the late luteal phase. Changes in appetite and eating behavior have been documented in women suffering from PMS, with an increased food intake occurring during the luteal phase. Moreover, in women with PMS, a major effect of the phase of the menstrual cycle on appetite has been documented and a high correlation with self-ratings of mood, particularly depression, has been described only in such disturbance. The aim of the present study was to analyse the clinical similarities between PMDD and Eating Disorders (in particular Bulimia Nervosa and Binge Eating Disorder). Thus, we compared the DSM III-R comorbidity, the personality dimensions and the eating attitudes in these patients, attempting to identify any relationship between groups. Twelve PMDD women (mean age 28 years), diagnosed using DSM IV criteria and premenstrual assessor form, were compared with 10 eating disorder (ED) women (6 Bulimia Nervosa, 4 Binge Eating Disorder) (mean age 25 years) and with 10 control women matched for age. The following instruments were used: (i) clinical interview with DSM III-R criteria (SCID); (ii) a psychometric study with TPQ for the evaluation of three personality dimensions (novelty seeking, harm avoidance and reward dependence); (iii) EAT/26 for the evaluation of eating attitudes. Results show that a high comorbidity for mood and anxiety disorders in PMDD and ED is well documented. Our PMDD patients share a 16.6% of comorbidity with ED, whereas such an association is present only in 2.3% of the general population. In addition, as a common clue, the personality dimension, harm avoidance, linked to a serotonin mediation is significantly more frequent in PMDD and ED than in normal controls. IN CONCLUSION: from the present study it seems clear that a certain degree of similarity exists between the PMDD and ED. However, whether or not these two disorders really share common ground from a physiopathological point of view still has to be clarified by more extensive studies.

Adolescent↗
PubMed1996

An assessment of hypothalamo-pituitary-adrenal axis functioning in non-depressed, early abstinent alcoholics.

Chronic alcohol consumption has been shown to be associated with abnormalities in the regulation of the hypothalamo-pituitary-adrenal (HPA) axis in humans. However, conflicting data exist in the literature, with particular regard to studies performed in actively drinking or withdrawn alcoholics; in addition, the frequent presence of depressive disturbances in such patients may importantly affect the neuroendocrine findings. In this study, we investigated HPA function in 12 male alcoholics, in whom the presence of depression and other possible confounding factors was excluded, during the first and second weeks after cessation of ethanol intake. The plasma corticotropin (adrenocorticotropic hormone, ACTH) and cortisol levels in response to both a stimulation test with human corticotrophin-releasing hormone (CRH; 100 micrograms IV) and an insulin (0.15 UI/kg IV)-induced hypoglycaemia (ITT) were measured; the cortisol response to a standard overnight dexamethasone (1 mg) suppression test (DST) was also tested. While the mean baseline ACTH and cortisol levels, measured in the morning (0800-0830 h), were not different from those of controls, ACTH and cortisol responses to the CRH test were markedly reduced (area of secretion p < .01 and p < .05, compared to controls). Similarly, the patient group showed an almost absent ACTH and cortisol release following insulin infusion (area of secretion p < .01 compared to controls, in either case). In four patients, non-suppression of plasma cortisol levels was seen on the DST, but no significant difference from normal suppressors was noted as far as the clinical features were concerned. These findings suggest that impaired hypothalamic and pituitary responsiveness, unrelated to depressive disturbances, occurs in recently withdrawn chronic alcoholics. While the possible influence of the alcohol withdrawal syndrome should be taken into account, such a pattern may be due to increased activity of the HPA axis, even in the face of preserved basal adrenal secretion. Whether these findings reflect a direct effect of sustained ethanol exposure on the components of the HPA axis, or a non-specific marker of impaired adaptation in chronic alcoholics, deserves further investigation.

Adrenocorticotropic Hormone↗
PubMed1996

Autonomic regulation of heart rate and peripheral circulation: comparison of high altitude and sea level residents.

1. To evaluate the activity of the autonomic nervous system on the heart and peripheral circulation in native high-altitude residents, during a Himalayan expedition we studied 12 men (age: 48 +/- 4, mean +/- SEM), life-long resident in a village at 4800 m (Sumdo village, Zanskar, India) and 7 healthy sea-level residents (age: 37 +/- 4) after 7 days of acclimatization (acclimatized lowlanders) at the same altitude. Furthermore 25 sea level residents (age: 46 +/- 2) underwent the same protocol at sea level. 2. R-R interval (RR), respiratory signal, non-invasive blood pressure, and skin arteriolar blood flow were evaluated in three different conditions: during free breathing in supine position and during controlled breathing (at 0.15 Hz), in supine and upright position, and analysed by autoregressive spectral analysis [low- (around 0.1 Hz) and high-frequency (respiratory) fluctuations, LF and HF, markers of sympathetic and vagal activity, respectively]. 3. High-altitude residents showed in supine position a higher RR than acclimatized lowlanders, similar to sea-level residents. RR variability was reduced in acclimatized lowlanders compared to both high-altitude residents and sea level residents. Systolic blood pressure (SBP) did not show significant differences between the three groups. High altitude residents showed in supine lower LF in RR signal compared to sea-level residents, and, compared to acclimatized lowlanders, higher HF and lower LF/HF ratio; high-altitude residents showed a reduction in skin microcirculation variability compared to sea-level residents, but this was eight fold greater than in acclimatized lowlander, thus indicating a much greater vasoconstriction in acclimatized lowlanders than in high-altitude residents. 4. In upright position, high-altitude residents showed the same behaviour as sea-level residents, with increase in LF-RR, and decrease in HF and LF-SBP. Acclimatized lowlanders showed similar directional trends though not significant changes for RR-LF. 5. After one week of acclimatization, lowlanders still manifested sympathetic activation and skin vasoconstriction; high-altitude residents did not show reduced vagal tone compared to sea-level residents, but a mild vasoconstriction appeared to be present. In conclusion, normal or enhanced vagal tone and preserved vasomotion are probably evidence of adaptation at high altitude hypoxia.

Adaptation, Physiological↗
PubMed1996

Effects of terguride on anterior pituitary function in parkinsonian patients treated with L-dopa: a double-blind study versus placebo.

In a randomized double-blind study, 20 parkinsonian patients (suffering from the disease for 2-18 years), chronically treated with levodopa (500-750 mg/day for 0.5-12 years), received terguride (1 mg b.i.d.) or placebo for 4 weeks. Growth hormone (GH), prolactin (PRL), thyroid-stimulating hormone (TSH), and insulin-like growth factor (IGF-I) secretions were studied before and after the morning dose of levodopa (250 mg p.o.), both before and at the end of study period. At the beginning of the study, basal hormonal levels were within normal limits, and levodopa administration induced a significant suppression in PRL and TSH levels (both p < 0.01)) and a significant increase in GH (p < 0.01). The same results were observed at the end of the study period in the placebo group. Addition of terguride induced a significant suppression in basal PRL levels (p < 0.01), whereas levodopa-induced hormonal changes were unaffected. These data suggest that the hypothalamic dopaminergic function that controls anterior pituitary hormones is preserved in parkinsonian patients, regardless of both the duration of the disease and the long-term treatment with levodopa. The strong additional prolactin-lowering effect of terguride indicates long-lasting dopaminergic effects, as is already known from hyperprolactinemic conditions. The dopaminergic effects of levodopa on TSH, GH, and IGF-I secretion were unchanged by terguride treatment. The anti-dopaminergic effects of terguride observed in the motor system in animal studies, as well as in levodopa-induced dyskinesias in parkinsonian patients, could not be observed in the case of the dopaminergic control of anterior pituitary hormones under the conditions of this study.

Aged↗
PubMed1995

Combined response of plasma and platelet catecholamines to different types of short-term stress.

Platelet catecholamines (CAs) do not seem to reflect the acute increases in plasma CAs observed during stress, at least over short periods of time. However, it is well known that stress, via the release of plasma CAs, is capable of affecting platelet function. To better address this issue, we studied platelet and plasma levels of free noradrenaline (NA), adrenaline (A), and dopamine (DA) in 10 healthy subjects undergoing three different stress tests: insulin tolerance test (ITT), cold pressor test (CPT) and handgrip test (HT). We also evaluated platelet count and platelet mean volume (MPV). ITT caused a considerable increase in plasma NA and a massive release of plasma A, while CPT and HT induced discrete increases only in plasma NA. ITT induced a significant decrease in platelet DA and a trend toward a decrease in platelet NA, along with a significant increase in MPV. All these changes occurred in coincidence with the peak levels of plasma CAs. No changes in platelet variables were observed in response to both CPT and HT. The modifications observed during ITT are likely to represent signs of an initial platelet activation in response to the acute plasma CA elevations this test was able to elicit. Our data show that platelet CA content does not represent a mere reflection of the circulating concentrations of plasma CAs, but it is the result of a dynamic balance between these two compartments.

Adult↗
PubMed1995

"Off" painful dystonia in Parkinson's disease treated with botulinum toxin.

The "off" painful dystonia (OPD), usually concerning the feet, is a type of abnormal involuntary movement, induced by the chronic use of levodopa. It is mostly observed in the advanced stage of Parkinson's disease (PD), particularly in the early morning, in the evening, and late at night. Indeed, some patients have experienced OPD also during "on" periods when dystonic posture of the foot alternates with dyskinesia. The pain probably is due to sustained muscle contraction, which causes prolonged muscle spasm, as in primary dystonia or torticollis. Dopaminergic drugs like bromocriptine, pergolide, and especially apomorphine (s.c. infusions, or bolus), can dramatically improve the OPD. Anticholinergics baclofen and lithium are alos used in the management of OPD with some benefit. On the other hand, clinical experience shows that in many cases, these therapeutic procedures are not always enough to produce the expected results. Thirty PD patients (22 men and eight women) with OPD of the foot were treated with botulinum toxin (Botox, Btx) using electromyograms to guide injections. Dystonia was evaluated using a quantitative rating scale. The selection of the muscles for Btx treatment was carried out on the basis of foot posture. We injected Btx into tibialis posterior, tibialis anterior, gastrocnemius, flexor digitorum longus, and extensores hallucis longus with a median dose 40 IU for each muscle, distributed in two sites. In all patients, the pain improved within 10 days, whereas in 21 patients, the pain disappeared completely for 4 months (range, 3-7 months); a concomitant improvement in intensity of the dystonic spasm was also observed. No side effects were reported. Seven patients with associated "on" foot dystonia described an improvement of foot posture on walking. In conclusion, in this uncontrolled study, the use of Btx in OPD seemed a promising tool to improve pain linked to foot dystonia; however, because of the well-known underlying dopaminergic defect in OPD, the Btx therapy should be considered only if the dopaminergic treatment established for the management of OPD has failed.

Aged↗