Biomedical subjects

M Cosentino

Publications and source records attributed to M Cosentino.

At least 19 recordsLinked to original sources

PubMed2006

Changes in autonomic modulation to the heart and intracellular catecholamines. A longitudinal study in differentiated thyroid carcinoma during short-term hypothyroidism and thyroid hormone replacement.

BACKGROUND: The effects of thyroid deprivation on the autonomic modulation to the heart remain controversial. METHODS: In this study in patients followed for thyroid carcinoma, we investigated (1) heart rate variability parameters and the baroreflex gain and (2) intracellular catecholamine levels in circulating lymphocytes during short-term hypothyroidism (phase 1) and after reinstitution of TSH-suppressive thyroid hormone replacement (phase 2). RESULTS: The RR interval value (p < 0.01) and systolic blood pressure (p < 0.05) were higher in phase 1 than in phase 2. The low-frequency/high-frequency (LF/HF) ratio was significantly lower in the hypothyroid state (p < 0.05), with a higher HF component (p < 0.05). After adjusting for mean RR interval in the regression model, the difference between the power of RR interval oscillations calculated in the two states was greater for the LF band (p = 0.005) and it was borderline significant for the HF band (p = 0.052). The baroreflex gain alpha(LF) index was similar in the two phases. The stimulus-induced cellular production of norepinephrine and epinephrine in peripheral blood mononuclear cells was significantly higher in phase 2. CONCLUSION: The neurally-mediated influences on the sinus node and the study of intracellular catecholamine production suggest a reduced sympathoexcitation in hypothyroidism compared with the treatment phase. The early increase in blood pressure observed after thyroid hormone withdrawal is not due to impaired sensitivity of the baroreflex arc.

Autonomic Nervous System↗

PubMed2005

Two patients with COMT inhibitor-induced hepatic dysfunction and UGT1A9 genetic polymorphism.

The authors report two cases of catechol-O-methyltransferase (COMT) inhibitor-induced asymptomatic hepatic dysfunction in women with Parkinson disease. The patients were genotyped for the UDP-glucuronosyltransferase (UGT) 1A9 gene (which encodes the main COMT inhibitor-metabolizing enzyme), and found to carry mutations leading to defective glucuronidation activity. This suggests that UGT1A9 poor metabolizer genotype(s) may be a predisposing factor for COMT inhibitor-induced hepatotoxicity.

Adult↗

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↗

PubMed2003

Effects of dopaminergic stimulation on peripheral markers of apoptosis: relevance to Parkinson's disease.

We investigated the effects of dopaminergic stimulation on anti-apoptotic protein Bcl-2, pro-apoptotic enzyme caspase- 3, and anti-oxidant/anti-apoptotic enzyme Cu/Zn superoxide dismutase (SOD) in human lymphocytes exposed to dopamine (DA). The same determinations were also carried out in parkinsonian patients treated with L-dopa. Caspase-3 activity and Cu/Zn SOD levels tended to increase when lymphocytes were exposed to low or intermediate doses of DA, while a decrease was observed, particularly in caspase-3 activity, with the higher DA dose. Bcl-2 levels were unaffected. In patients, we observed a negative correlation between Cu/Zn SOD levels and daily intake of L-dopa, which also tended to be negatively correlated with caspase-3 activity, but not with Bcl- 2. Our results show that dopaminergic stimulation is associated with complex changes in regulatory proteins of apoptosis.

Adult↗

PubMed2003

Peripheral markers of apoptosis in Parkinson's disease: the effect of dopaminergic drugs.

In this study, we measured the lymphocyte levels of proteins involved in apoptosis regulation, such as Bcl-2, the peripheral benzodiazepine receptor (PBR), caspase-3, and Cu/Zn superoxide dismutase (Cu/Zn SOD), in patients with Parkinson's disease (PD), either untreated or under therapy with dopaminergic agents (l-Dopa alone or l-dopa + dopamine agonists) and in healthy volunteers. All PD groups showed increased activity of caspase-3, compared to controls, particularly those under treatment only with l-Dopa. In this latter group, the increase in caspase-3 activity was also paralleled by an increase in the concentration of Cu/Zn SOD. In addition, patients taking l-Dopa + dopamine agonists showed marked decrease in Bcl-2 levels and increased PBR expression, which seems in keeping with the hypothesis that PBR may be functionally related to Bcl-2. In conclusion, we found clear modifications in the levels of proteins involved in the control of apoptosis in lymphocytes of PD patients. These changes were disease related but also modulated by the pharmacological treatment, which confirms the potential role of apoptosis in PD pathogenesis and the modulatory influence of dopaminergic agents.

Analysis of Variance↗

PubMed2002

[Anxiety and acceptance of gynecological laparoscopic operations].

BACKGROUND: To evaluate the acceptance of gynecological laparoscopic operations. METHODS: A comparative analysis has been performed in a group of 32 women by analyzing a) the cognitive component, by means of 2 questionnaires administered before and after the operation and b) the emotional component, by evaluating the pre- and post-operative anxiety levels (State anxiety) and the constitutional ones (Trait anxiety) using the STAI Y test. The anxiety level of our group has been compared with that attributed to the general population by means of the Z test. Moreover, significant correlations have been searched between: 1) pre- and postoperative Trait and State anxiety, through the Pearson's correlation test; 2) the variables investigated by the two informational questionnaires and the anxiety measures, through the Student t test; 3) the informative variables themselves through the c2 test. RESULTS: Postoperative State anxiety is lower than that of the general population (p<0.05); a significant correlation exists between post- operative State and Trait anxiety (p<0.05); Trait anxiety is higher when fantasies linked to the operation are characterized by fear (p<0.05), and attribution of the decision to operate to the doctor (p<0.05); post-operative State anxiety is higher when the level of education is low (p<0.05) and the attribution of the decision to operate is to the doctor (p<0.05); a significant correlation exists between fantasies characterized by fear and the experience of postoperative pains, between postoperative pains and attribution of the decision to operate to the doctor (p<0.05) and between fantasies characterized by fear and attribution of the decision to operate to the doctor (p<0.05). CONCLUSIONS: Higher anxiety levels have been detected in the pre-operative phase, in less educated patients and when the decision to operate has been attributed to the doctor. A not wholly convinced personal attitude has been accompanied by preoperative fantasies characterized by fear and has resulted in subjectively more painful postoperative course.

Adolescent↗

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

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

Anti-HIV agents 45(1) and antitumor agents 205.(2) two new sesquiterpenes, leitneridanins A and B, and the cytotoxic and anti-HIV principles from Leitneria floridana.

Two new sesquiterpenes, leitneridanin A (1) and leitneridanin B (2), and seven known compounds, lirioresinol B, (-)-pinoresinal, (+)-lariciresinol, quassimarin (3), simalikalactone D (4), 1-methoxycanthinone (5), and 5-methoxycanthinone (6), were isolated from Leitneria floridana. Their structures were identified on the basis of spectral data. In vitro biological evaluation showed that 5 is a potent anti-HIV agent (EC(50) 0.26 g/mL; TI >39) and that 3-6 suppressed the growth of a panel of human tumor cell lines (KB, A-549, HCT-8, CAKI-1, MCF-7, and SK-MEL-2). Compounds 3 and 4 were significantly active, with ED(50) values in the range of 0.26-0.012 g/mL.

Anti-HIV Agents↗

PubMed2000

[Psychologic consequences of a case of aortic perforation during an intervention of laparoscopic surgery].

Although rare, the severe complications inherent in the laparoscopic technique can be physically devastating, whereas from a psychological point of view they may be very traumatic because they are perceived by the patient as unexpected and totally out of proportion compared to the perceived expectation of risk prior to surgery. The possible psychological consequences of a case of aortic perforation with cardiac arrest were evaluated using the Rorschach test in a patient who had undergone exploratory laparoscopy for secondary amenorrhea. An analysis of the test did not show psychotraumatic data attributable with certainty to this experience.

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

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↗

PubMed1999

Endogenous catecholamine synthesis, metabolism, storage and uptake in human neutrophils.

Evidence is presented that human neutrophils contain catecholamines and several of their metabolites. In vitro, incubation with alpha-methyl-p-tyrosine or pargyline affects intracellular dopamine, norepinephrine and their metabolites, suggesting catecholamine synthesis and degradation by these cells. Reserpine reduces intracellular dopamine and norepinephrine and desipramine reduces intracellular norepinephrine, suggesting the presence of storage and uptake mechanism. In view of the ability of catecholamines to affect neutrophil function, the present results support the hypothesis that autoregulatory adrenergic mechanisms may exist in these cells.

Adult↗

PubMed1999

Modulation of enteric cholinergic neurons by hetero- and autoreceptors: cooperation among inhibitory inputs.

In the guinea-pig colon, acetylcholine (ACh) release from intrinsic cholinergic motor neurons is inhibited by adrenoceptors, opioid and muscarinic receptors. Chronic sympathetic denervation resulted in supersensitivity to the inhibitory effect of DAMGO (mu-opioid agonist) on ACh release and on the peristaltic reflex. After chronic treatment with naltrexone (NTX) supersensitivity to DAMGO and subsensitivity to UK14,304 (alpha2-adrenoceptor agonist) developed for both functional parameters. The facilitatory effect of scopolamine on ACh release remained unchanged after chronic NTX treatment, whereas it was potentiated after chronic sympathetic denervation. These data suggest the existence of a functional interaction between different inhibitory pathways modulating cholinergic motor neurons in the guinea-pig colon. Namely, chronic manipulation of an inhibitory pathway may entail adaptive sensitivity changes in another inhibitory pathway so that homeostasis can be maintained.

Acetylcholine↗