Biomedical subjects

G Frigo

Publications and source records attributed to G Frigo.

At least 19 recordsLinked to original sources

PubMed2004

Modifications of apoptosis-related protein levels in lymphocytes of patients with Parkinson's disease. The effect of dopaminergic treatment.

In this study, we investigated whether changes in the regulatory mechanisms of apoptosis and oxidative stress may be detected, peripherally, in patients with Parkinson's disease (PD). For this purpose, we measured caspase-3 activity, Bcl-2 concentrations, peripheral benzodiazepine receptor (PBR) expression and Cu/Zn superoxide dismutase (SOD) concentrations in lymphocytes of untreated PD patients, patients treated only with L-Dopa or with L-Dopa and dopamine agonists and healthy volunteers. Caspase-3 activity was significantly increased in all PD patient groups. Patients treated with L-Dopa and dopamine agonists showed the lowest values of Bcl-2, coupled with the highest density of PBRs, while increased levels of Cu/Zn SOD were found in the group under monotherapy with L-Dopa. We also found, in PD patients, clear, negative correlations between Bcl-2 levels and both duration and severity of the disease. Our findings point to the existence of changes in the regulatory mechanisms of apoptosis in PD patients -- observable outside the central nervous system -- which seem to be modulated by the pharmacological treatment with dopaminergic agents.

Aged↗

PubMed2004

Triptans and gastric accommodation: pharmacological and therapeutic aspects.

In the past decade, several studies have reported a significant delay of gastric emptying induced by the anti-migraine agent sumatriptan (a 5-hydroxytryptamine (5-HT)1B/D receptor agonist) in healthy human beings. In patients with functional dyspepsia, sumatriptan improves gastric accommodation after food consumption and reduce perception of gastric distension, hence relieving epigastric symptoms. Recent studies have established that impaired accommodation after food consumption is a major patho-physiological mechanism in functional dyspepsia and restoration of accommodation is considered to be a potential therapeutic target. The precise site of action of sumatriptan in humans is at present unknown, although recent studies carried out using a canine model indicate that sumatriptan exerts its action on gastric accommodation through 5-HT1B receptors, since both GR127935 and SB216641 (respectively, non selective 5-HT1B/D and selective 5-HT1B receptor antagonists) fully antagonised the effects of sumatriptan. Gastric relaxation and enhanced accommodation to a distending stimulus seem to be a class effect of triptans, since it occurs not only with sumatriptan, but also with second-generation triptans (rizatriptan and naratriptan), at least in a canine model. In dyspeptic patients, administration of triptans would be able to restore gastric accommodation after a meal and to improve symptoms of early satiety, confirming the therapeutic potential of 5-HT1B/D receptor agonists in functional dyspepsia.

Animals↗

PubMed2002

P2 receptors in the murine gastrointestinal tract.

The actions of adenosine, adenosine 5'-triphosphate (ATP), 2-methylthio adenosine diphosphate ADP (2-MeSADP), 2-methylthio ATP (2-MeSATP), alpha,beta-methylene ATP (alpha,beta-meATP) and uridine triphosphate (UTP) on isolated segments of mouse stomach (fundus), duodenum, ileum and colon were investigated. The localization of P2Y(1), P2Y(2), P2Y(4), P2X(1) and P2X(2) receptors and neuronal nitric oxide synthase (NOS) were examined immunohistochemically, and P2Y(1) mRNA was examined with in situ hybridization. The order of potency for relaxation of longitudinal muscle of all regions was: 2-MeSADP>/=2-MeSATP>alpha,beta-meATP>ATP=UTP=adenosine. This is suggestive of P2Y(1)-mediated relaxation and perhaps a further P2Y receptor subtype sensitive to alpha,beta-meATP. As ATP and UTP are equipotent, the presence of a P2Y(2) receptor is indicated. ATP responses were inhibited by the P2Y(1)-selective antagonist MRS 2179, and suramin. P2Y(1) receptors were visualized immunohistochemically in the smooth muscle of the ileum and in a subpopulation for myenteric neurones, which also stained for NOS. P2Y(1) mRNA was localized in neurones in both myenteric and submucosal ganglia in the ileum. Taken together, these results suggest that ATP was acting on non-adrenergic, non-cholinergic inhibitory neurons, which release both nitric oxide (NO) and ATP. Reduced relaxations to 2-MeSADP by tetrodotoxin and N(omega)-nitro-L-arginine methyl ester, are consistent with this possibility. Adenosine acts via P1 receptors to relax smooth muscle of the mouse gut. Segments of mouse colon (in contrast to the stomach and small intestine) were contracted by nucleotides with the potency order: 2-MeSATP>alpha,betameATP>ATP; the contractions showed no desensitization and were antagonized by suramin and PPADS, consistent with responses mediated by P2X(2) receptors. Immunoreactivity to P2X(2) receptors was demonstrated on both longitudinal and circular muscle of the colon, but not in the other regions of the gut, except for a small subpopulation of myenteric neurones. In summary, neuronal P2Y(1) receptors appear to mediate relaxation, largely through NO in all regions of the mouse gut, and to a lesser extent by P2Y(1), P2Y(2) and a novel P2Y receptor subtype responsive to alpha,beta-meATP in smooth muscle, while P2X(2) receptors mediate contraction of colonic smooth muscle.

Animals↗

PubMed2002

Effects of physical exercise on clinic and 24-hour ambulatory blood pressure in young subjects with mild hypertension.

BACKGROUND: The aim of the study was to assess the effect of physical activity on 24-hr ambulatory blood pressure (ABPM) and office blood pressure (BP) in 572 male subjects with borderline to mild hypertension from the HARVEST study. METHODS: Subjects were 18 to 45 years old with diastolic BP of 90-99 mmHg and/or systolic BP of 140-159 mmHg. They never took any anti-hypertensive therapy. All subjects underwent physical examination, office BP measurement and two 24-hr ambulatory BP monitorings performed three months apart. Subjects were classified as non exercisers, group 1 (n=331), mild exercisers, group 2 (n=192) and heavy exercisers, group 3 (n=49). During the three months of follow-up subjects maintained the same physical activity habits. There was no difference in smoking and alcohol consumption between the 3 groups. As the groups differed significantly in age and body mass index data were adjusted for these confounders. RESULTS: At baseline office and ambulatory systolic BP were similar in the 3 groups, while diastolic BP was proportional to the level of physical activity although the difference was significant only between the group of non-exercisers and mild exercisers. Heart rate (HR) was always inversely related to the intensity of exercise. After three months follow-up office systolic BP was similar among the three groups and diastolic BP slightly decreased in the exercisers (group 1 vs group 3 p=0.02, group 2 vs group 3 p=0.04). At ABPM the group of heavy exercisers showed a significant decrease in daytime systolic BP (135.4plus minus0.6 vs 134plus minus0.8 vs 132.2plus minus1.6 mmHg; group 1 vs group 3 p<0.05) and the difference between systolic ambulatory BP at the 3rd month and at baseline, showed an additional significant decrease according to exercise intensity (24-hr systolic BP group 1 vs group 3 p=0.001, group 2 vs group 3 p=0.004; daytime systolic BP group 1 vs group 3 p=0.0009, group 2 vs group 3 p=0.004; night-time systolic BP group 1 vs group 3 p=0.02, group 2 vs group 3 p=0.02). No changes in ambulatory diastolic BP were observed. CONCLUSIONS: In conclusion, physical activity has a positive effect in lowering BP attenuating the risk of hypertension in young subjects with borderline hypertension. The anti-hypertensive effect of physical activity persisted after three months and the group of exercisers had an additional reduction in systolic BP detected by ABPM. To obtain accurate information on chronic levels of arterial pressure over time 24-hr ambulatory BP should be preferred to traditional casual readings.

Adolescent↗

PubMed2001

Gastric motor effects of triptans: open questions and future perspectives.

Sumatriptan is a 5-HT1B/D receptor agonist of documented efficacy in relieving migraine and associated symptoms such as nausea and vomiting. In the past decade, several studies reported an important delay of gastric emptying induced by sumatriptan in healthy humans. The impact of this gastric motor effect of sumatriptan in migraineurs is difficult to predict: a further delay in gastric emptying could be detrimental (i.e. increased nausea and epigastric symptoms) in patients already having delayed gastric emptying. However, in patients with functional dyspepsia, sumatriptan is also reported to improve gastric accommodation to a meal and reduce perception of gastric distention, hence relieving epigastric symptoms. Thus, reduced visceral perception could be a mechanism involved in reducing nausea during a migraine attack. Paradoxically, sumatriptan is reported both to relieve the nausea of a migraine attack and to have nausea as a side effect. Although careful analysis of the time of onset of nausea may offer a clue as to the origin of this symptom, available data do not support definite conclusions, all the more so because the gastric motor effect of second-generation triptans are still unexplored. Taken together, the available evidence warrants further studies to clarify the following issues: first, the mechanism responsible for the gastric motor effect of sumatriptan [receptor subtype(s) involved; central vs peripheral mechanism]; secondly, the effects on gastric motility/visceral sensitivity of second-generation triptans (which are 5-HT1B/D receptor agonists) and more recent selective 5-HT1D receptor agonists (proposed as investigational antimigraine agents with less potential to induce coronary vasoconstriction through 5-HT1B receptors); finally, the possible use of drugs improving gastric accommodation to a meal in the management of those dyspeptic patients with impaired fundic relaxation/altered visceral sensitivity.

Forecasting↗

PubMed2001

Increased reporting of adverse reactions to ACE inhibitors associated with limitations to drug reimbursement for angiotensin-II receptor antagonists.

BACKGROUND AND AIM: From February 1998 to September 1999, the Italian Ministry of Health limited angiotensin-II type-1 (AT1) receptor antagonist reimbursement only to patients who necessitated discontinuation of angiotensin converting enzyme (ACE) inhibitor treatment due to cough or angioedema. We assessed the consequences of this decision on the reporting of ACE inhibitor-associated adverse drug reactions (ADRs). METHODS: ACE inhibitor-associated ADRs reported to the national pharmacovigilance system in 1997-2000 in the district of Varese (northern Italy, more than 820,000 inhabitants) were retrieved and analysed. The dispensation of ACE inhibitors and AT, receptor antagonists reimbursed by the National Health System was also examined. RESULTS: There were 228 reports of ACE inhibitor-associated ADRs, and cough was the ADR reported in 93.4% of cases. There were no reports of cough in 1997, 50 in 1998, 156 in 1999 and 7 in 2000. In 1998-1999, the dispensation of ACE inhibitors showed little variation, while that of AT1 receptor antagonists grew about twofold. CONCLUSIONS: There was a clear correlation between ACE inhibitor-associated ADR reporting and limitation to AT1 receptor antagonist reimbursement status. Drug reimbursement policies should thus be added to the list of factors that may bias ADR reporting, and health authorities should be aware of this potential bias when defining specific measures to regulate prescription and use of new drugs.

Adult↗

PubMed2001

Left ventricular contractile performance in the early stage of hypertension in humans.

The aim of the present study was to assess how cardiac structural changes contribute to increasing left ventricular pump function during exercise in subjects with mild hypertension. In 23 young male subjects with mild hypertension and 12 male normotensive control subjects, left ventricular function was measured echocardiographically using the fractional shortening/ meridional stress relationship at rest and during longlasting exercise at the anaerobic threshold. Mean exercise duration and intensity were 61 (SEM 1.7) min and 71.3 (SEM 2.5)% VO2max (maximal oxygen uptake), respectively, in the hypertensive subjects, and 63 (SEM 1.5) min and 75.7 (SEM 2.2)% VO2max, respectively, in the normotensive subjects (all differences= n.s.). Left ventricular fractional shortening was measured both at the endocardium and at the midwall. In the hypertensive subjects the endocardial fractional shortening, predicted on the basis of the shortening/stress relationship in the normotensive controls, overestimated midwall fractional shortening throughout rest (P=0.04) and exercise (P=0.004). To study how an increase in left ventricular wall thickness contributed to increasing ejection performance during exercise, the hypertensive subjects were divided according to whether their relative wall thickness was less than 0.35 or equal to or greater than 0.35. Subjects with relative wall thicknesses equal to or greater than 0.35 had a depressed myocardial contractility at rest (P=0.0001). During exercise they increased their stroke volume and cardiac output adequately through an increase in ejection performance, while myocardial contractility remained subnormal (P < 0.0001). In conclusion, the present results indicated that in mildly hypertensive subjects an increased left ventricular wall thickness is crucial in preserving left ventricular pump function during exercise.

Adult↗

PubMed2001

G protein beta3 subunit gene 825T allele is associated with increased left ventricular mass in young subjects with mild hypertension.

BACKGROUND: A nucleotide substitution (C-->T) at position 825 of the gene GNB3 encoding the beta3 subunit of heterotrimeric G proteins is associated with alternative splicing and enhanced signal transduction. There is accumulating evidence from different populations that the 825T allele is associated with increased prevalence of hypertension, obesity, and left ventricular hypertrophy. However, it is unclear to what extent the 825T allele has a direct influence on left ventricular structure, independently of the effects of pressure and body mass index. Therefore we explored whether the GNB3 825T allele is associated with increased left ventricular mass index in a selected and homogeneous group of young, never treated, mild hypertensives. PROCEDURES: Young subjects (n = 207, aged 18 to 45 years) were genotyped at the GNB3 825 locus. In each patient, 24-h ambulatory blood pressure (BP) measurement and two-dimensional guided M-mode echocardiography combined with Doppler sonography were performed. RESULTS: The genotype distribution among patients was in Hardy-Weinberg equilibrium. Patients carrying the 825T allele had an increased left ventricular mass index (95.1 +/- 1.5 v 89.7 +/- 1.5 g/m2; P = .01) in comparison to those with CC genotype. The association between left ventricular mass index and 825T allele was independent of gender, age, BP, heart rate, alcohol intake, and physical activity. CONCLUSIONS: In young patients with mild hypertension without heart disease the 825T allele is associated with an increased left ventricular mass index. These hypothesis-generating data suggest that GNB3 825T allele may be considered as one genetic marker predisposing to an increase in left ventricular mass in hypertensives, and justifies larger studies.

Adult↗

PubMed2001

Early signs of cardiac involvement in hypertension.

BACKGROUND: Whether abnormalities of diastolic function are the earliest cardiac change in hypertension is still a matter for dispute. The aim of this study was to assess whether left ventricular diastolic dysfunction is an early sign of cardiac involvement in hypertension. METHODS: In 578 young patients with stage I hypertension from the Hypertension and Ambulatory Recording Venetia Study (HARVEST) and 101 normotensive control patients echocardiographic Doppler examination and ambulatory blood pressure monitoring were performed. RESULTS: Left ventricular mass, wall thickness, and relative wall thickness, adjusted for confounders, were greater in the hypertensive than in the normotensive patients (all P <.0001). After adjustment for confounders, the A-wave peak velocity was higher in the hypertensive patients (51.5 +/- 11.5 vs 43.4 +/- 8 cm/s, P <.001) as were A-wave velocity time integral (5.6 +/- 1.7 vs 4.6 +/- 1.3 cm, P =.01), total area (16.9 +/- 4.4 vs 15.6 +/- 3.1 cm, P =.04), and E-wave peak velocity (69.9 +/- 15.2 vs 67.5 +/- 13.3 cm/s, P =.03). All indexes of diastolic function were similar in the hypertensive subjects subdivided according to whether they had "white-coat" or sustained hypertension. Among the hypertensive subjects, age and heart rate were the strongest predictors of diastolic indexes, whereas ambulatory blood pressure explained only a marginal part of the E/A ratio, A-wave peak velocity, and the first one third total area ratio (P =.04, P =.02, and P =.05, respectively). Left ventricular mass and wall thickness were not associated with any Doppler index. When a clustering of diastolic indexes (E/A wave ratio, deceleration time, first one third of diastole, and peak E-wave-velocity) was used to identify subjects with diastolic dysfunction, no significant differences in either clinic or ambulatory blood pressure were observed between the group with diastolic dysfunction and the group with normal function. CONCLUSIONS: We conclude that the earliest signs of cardiac involvement in hypertension are left ventricular structural abnormalities. Left ventricular diastolic function is only marginally affected, even when multiple parameters of left ventricular filling are taken into account.

Adult↗

PubMed2001

Diazepam stimulates migration and phagocytosis of human neutrophils: possible contribution of peripheral-type benzodiazepine receptors and intracellular calcium.

In isolated human neutrophils, diazepam (10 nmol/l to 10 micromol/l) concentration-dependently increased migration and phagocytosis. Diazepam-induced migration and phagocytosis were inhibited by the peripheral benzodiazepine receptor (PBR) antagonist PK11195 (10 micromol/l). The PBR agonist Ro5-4864 (10 nmol/l to 10 micromol/l) did not affect migration but slightly enhanced phagocytosis, while clonazepam, which binds to the central-type benzodiazepine receptors but has no affinity for PBRs, was ineffective on both parameters up to 10 micromol/l. Phagocytosis induced by diazepam or Ro5-4864 was inhibited by the Ca2+ channel blocker L-verapamil (10 micromol/l), which however did not affect the action of diazepam on migration. Competition binding experiments performed by fluorescent staining of PBRs showed that diazepam directly interacts with PBRs on human neutrophils. Both diazepam and Ro5-4864 (10 nmol/l to 10 micromol/l) induced a rise of intracellular free Ca2+ concentrations ([Ca2+]i), which was inhibited by PK11195 (10 micromol/l) and L-verapamil (10 micromol/l) and prevented by extracellular Ca2+ chelation with EGTA (5 mmol/l). In conclusion, experimental evidence indicates that in human neutrophils diazepam stimulates both migration and phagocytosis through activation of PBRs. Diazepam-induced [Ca2+]i changes depend on a PBR-operated, L-verapamil-sensitive increase in the plasma membrane permeability and subsequent extracellular Ca2+ entry, and contribute to diazepam-induced phagocytosis. On the contrary, the effect of diazepam on migration seems to occur through Ca2+ -independent mechanisms.

Calcium↗

PubMed2000

HPLC-ED measurement of endogenous catecholamines in human immune cells and hematopoietic cell lines.

A rapid and simple HPLC-ED method is described to identify and measure catecholamines (CTs) and their major metabolites in immune cells. Using this method, intracellular CTs were quantified in human peripheral blood mononuclear cells (PBMCs), T and B lymphocytes, monocytes and granulocytes. Immune cell subsets were separated by density gradient centrifugation and immunomagnetic cell sorting. CTs were also found in the human hematopoietic cell lines NALM-6 (pre-B) and (in smaller amounts) in Jurkat (T lymphoblastoid) and U937 (promonocytic). In cultured PBMCs, intracellular CTs were reduced by both the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine and the chromaffin granule depletant reserpine. In NALM-6 cells, both alpha-methyl-p-tyrosine and the dopamine-beta-hydroxylase inhibitor disulfiram reduced intracellular CTs, supporting the presence of active synthetic pathways in these cells. Since sympathoadrenergic mechanisms play a key role in the interactions between the immune system and the nervous system, these findings may be relevant for a better understanding of the neuro-immune network.

B-Lymphocytes↗

PubMed2000

Glutamate receptors of the AMPA type modulate neurotransmitter release and peristalsis in the guinea-pig isolated colon.

To assess the role of AMPA and kainate receptors in modulating neurotransmitter release from the myenteric plexus, the effect of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and kainic acid on endogenous acetylcholine (ACh) and noradrenaline (NA) overflow from the guinea-pig isolated colon was studied. AMPA inhibited spontaneous ACh overflow and increased electrically-evoked NA overflow. Kainic acid did not influence both ACh and NA overflow. AMPA-mediated effects on ACh and NA overflow were significantly reduced by the AMPA/kainate antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione, CNQX. The inhibitory effect of AMPA on ACh overflow could be due, at least in part, to the AMPA-induced NA overflow as it was greatly reduced after adrenoceptor blockade and virtually abolished in sympathetically-denervated animals. The possible functional significance of these findings was studied by measuring the efficiency of the peristaltic reflex in the presence of the different agonists. The efficiency of peristalsis was enhanced by AMPA, whereas it was not modified by kainic acid. In conclusion, AMPA receptors, but not kainate receptors, may play a role in the modulation of ACh and NA release and of peristalsis in the guinea-pig colon.

Acetylcholine↗

PubMed2000

Diazepam-binding inhibitor-derived peptides induce intracellular calcium changes and modulate human neutrophil function.

We studied the effects of two diazepam-binding inhibitor (DBI)-derived peptides, triakontatetraneuropeptide (DBI 17-50, TTN) and eiksoneuropeptide (DBI 51-70, ENP), on cytosolic free Ca2+ concentrations ([Ca2+]i), chemotaxis, superoxide anion (O2-) generation, and phagocytosis in human neutrophils. Both TTN and ENP induced a rapid and transient rise of [Ca2+]i. The effect of TTN depended on the presence of extracellular Ca2+, whereas the effect of ENP also persisted after extracellular Ca2+ chelation. TTN induced neutrophil chemotaxis, stimulated O2- generation, and enhanced phagocytosis. ENP did not affect cell migration and oxidative metabolism but enhanced phagocytosis. Both peptides modulated N-formyl-methionyl-leucyl-phenylalanine- and phorbol myristate acetate-induced O2- generation. Because neutrophils express benzodiazepine receptors of the peripheral type (pBRs) and DBI-derived peptides may interact with such receptors, we investigated the possible role of pBRs in TTN- or ENP-induced effects. The synthetic pBR ligand RO 5-4864 increased [Ca2+]i through extracellular Ca2+ influx and this effect was prevented by the pBR antagonist PK-11195. RO 5-4864, however, was ineffective on neutrophil migration and O2- generation and only slightly affected phagocytosis. Moreover, PK-11195 delayed the [Ca2+]i rise induced by TTN but did not significantly affect its extent, and had no effect on the [Ca2+]i rise induced by ENP. We conclude that DBI-derived peptides induce [Ca2+]i changes and modulate neutrophil function mainly through pBR-independent pathways. In view of the wide cell and tissue distribution of DBI in the brain and in peripheral organs, modulation of neutrophil function by DBI-derived peptides may be relevant for both the neuroimmune network and the development and regulation of the inflammatory processes.

Antineoplastic Agents↗

PubMed2000

An approach for the estimation of drug prescribing using the defined daily dose methodology and drug dispensation data. Theoretical considerations and practical applications.

OBJECTIVE: To test the hypothesis that comparison of defined daily dose (DDD) and drug user data may help to estimate drug exposure in a defined population and provide information about drug prescribing patterns. METHODS AND RESULTS: First, comparison of DDD figures with the number of apparent drug users (ADU, i.e., individuals for whom at least one prescription of the drug had been dispensed during a given time period) is demonstrated to correspond to the product of the prescribed daily dose (PDD) and the proportion of days in which the drug had been taken (days of treatment/days in a time period, D). The resulting equation (DDD/day)/ ADU in a time period = PDD x D is then applied to the analysis of different sets of drug dispensation data. Examples show that this approach may be helpful to monitor drug prescribing patterns over time. Moreover, in definite situations, it may provide reliable estimates of either PDD or D. CONCLUSIONS: Comparison of DDD and drug user data is suggested to be a cost-effective strategy to monitor drug prescribing patterns from an epidemiological perspective, which may be useful to researchers involved in drug utilisation studies as well as to health authorities for monitoring and regulatory purposes.

Algorithms↗

PubMed2000

Reproducibility of heart rate measured in the clinic and with 24-hour intermittent recorders.

This study was undertaken to assess the reproducibility of office versus ambulatory heart rates in 839 hypertensive subjects participating in the Hypertension and Ambulatory Recording Venetia Study (HARVEST). A 24-hour heart rate was recorded twice; this procedure was repeated three months later. Reproducibility was better for ambulatory than for office measurement, and was greater for 24-hour than for daytime heart rate, and lowest for night-time heart rate. Reproducibility of office heart rate was impaired above 85 bpm, and was poorer in subjects with more severe office hypertension. A small but significant decrease in average daytime (-1 bpm, P < 0.0001) and virtually no change in night-time heart rate (-0.3 bpm, NS) were observed at repeat recording. Heart rate reproducibility indices were related to the extent of the heart rate and blood pressure white-coat effect, but did not vary according to age, gender, body mass index, day-night blood pressure difference, or alcohol or tobacco use. Results indicate that heart rate recorded over the 24 hours has a better reproducibility than office heart rate, and could thus be a better prognostic indicator than traditional measurement of resting heart rate in the hospital setting.

Adult↗

PubMed1999

Hospital-based survey of doctors' attitudes to adverse drug reactions and perception of drug-related risk for adverse reaction occurrence.

Doctors' attitudes to adverse drug reactions (ADRs) and perception of drug-related risk for ADR occurrence were investigated in four hospitals in Northern Italy using an interviewer-administered questionnaire. ADRs were a relevant concern in medical practice for 80% of the respondents and had been observed by 87%. ADRs were perceived to occur in no more than 5% of hospitalized patients and serious ADRs in less than 1%. The response patterns, however, differed according to the ward of work and the year of graduation of the doctors. Antibacterials, NSAIDs and antiarrhythmics were rated as higher risk drugs, while diuretics, lipid lowering agents, antihistamines, antiemetics and antispasmodics were rated as lower risk drugs. Risk perception was dishomogeneous mainly with respect to the ward of work. The estimated frequency of ADR occurrence, the perception of drug-related risk and previous ADR reporting behaviour were clearly correlated. The present results suggest that personal factors affect doctors' attitudes to ADRs, perception of drug-related risk and ADR reporting behaviour and may thus be relevant in developing and targeting educational strategies aimed at increasing awareness of ADRs and at encouraging ADR reporting.

Journal Article↗

PubMed1999

Atypical beta-adrenoceptors mediating relaxation in the human colon: functional evidence for beta3-rather than beta4-adrenoceptors.

The aim of the present functional study was to assess the role of beta3-adrenoceptors in the light of recent findings suggesting the existence of a putative fourth beta-adrenoceptor in adipose and heart tissue. The effect of the non-conventional beta3-adrenoceptor partial agonist CGP12177A is resistant to the effect of the beta3-adrenoceptor antagonist SR59230A. Under isotonic conditions in circular muscle strips of human distal colon, the concentration-effect relationship of CGP12177A and SR59104A (beta3-adrenoceptor agonists), alone and in the presence of CGP20712A (beta1-adrenoceptor antagonist) ICI118551 (beta2-adrenoceptor antagonist) and SR59230A, all 0.1 microm was studied. CGP12177A concentration-dependently relaxed circular muscle strips (pEC50=6.16+/-0.05). This effect was left unchanged by beta1-/beta2-adrenoceptor blockade, but antagonised by SR59230A (pA2=8.12+/-0.02). SR59104A concentration-dependently relaxed circular muscle strips (pEC50=5.43+/-0.01), an effect that was not significantly affected by pretreatment with CGP20712A and ICI118551, but competitively antagonised by SR59230A (p KB=7.89). Isoprenaline-induced relaxations were antagonised by propranolol with a low pA2value (7.76+/-0.16). These results provide further evidence for the presence of functional beta3-adrenoceptors in the human colon, but do not support a role for an atypical beta-adrenoceptor distinct from the beta3-subtype.

Adrenergic beta-Agonists↗

PubMed1999

Plasticity in the enteric nervous system.

Enteric ganglia can maintain integrated functions, such as the peristaltic reflex, in the absence of input from the central nervous system, which has a modulatory role. Several clinical and experimental observations suggest that homeostatic control of gut function in a changing environment may be achieved through adaptive changes occurring in the enteric ganglia. A distinctive feature of enteric ganglia, which may be crucial during the development of adaptive responses, is the vicinity of the final effector cells, which are an important source of mediators regulating cell growth. The aim of this review is to focus on the possible mechanisms underlying neuronal plasticity in the enteric nervous system and to consider approaches to the study of plasticity in this model. These include investigations of neuronal connectivity during development, adaptive mechanisms that maintain function after suppression of a specific neural input, and the possible occurrence of activity-dependent modifications of synaptic efficacy, which are thought to be important in storage of information in the brain. One of the applied aspects of the study of plasticity in the enteric nervous system is that knowledge of the underlying mechanisms may eventually enable us to develop strategies to correct neuronal alterations described in several diseases.

Adaptation, Biological↗