Biomedical subjects

D Esposti

Publications and source records attributed to D Esposti.

At least 19 recordsLinked to original sources

PubMed2004

Effect of multiple doses of clarithromycin and amoxicillin on IL-6, IFNgamma and IL-10 plasma levels in patients with community acquired pneumonia.

Inflammation is crucial for the pathogenesis of both infectious and chronic obstructive pulmonary diseases. It is therefore important to modulate pulmonary inflammation in patients with these lung disorders. Macrolide antibiotics modulate inflammation in vitro and in in vivo by inhibiting the production of proinflammatory cytokines and prostaglandin E2, neutrophil chemotactic activity and elastase activity. This study evaluates the effect of clarithromycin (500 mg b.i.d. x 7 days) in comparison to amoxicillin (1 g t.i.d. x 7 days) in patients with community acquired pneumonia by testing plasma levels of IL-6, IFNgamma and IL-10 before starting therapy and at the 3rd and 7th days of therapy. Clarithromycin significantly decreased plasma levels of IL-6 and significantly increased those of IFNgamma and IL-10 at the 3rd and 7th day in comparison to basal levels. In patients treated with amoxicillin a significant decrease in IL-6 plasma levels was observed at the 7th day of therapy, probably in relation to the resolution of inflammatory symptoms. In the same patients IFNgamma plasma levels decreased during treatment while IL-10 plasma levels were unaffected.

Administration, Oral↗

PubMed2002

Impact of perioperative haemodynamic monitoring on cardiac morbidity after major vascular surgery in low risk patients. A randomised pilot trial.

OBJECTIVE: to evaluate whether perioperative haemodynamic optimisation influences outcome from infrarenal abdominal aortic aneurysm repair. METHODS: a consecutive series of 100 eligible patients were randomised to either haemodynamic optimisation through the use of a pulmonary artery catheter (CI > 3.0 l/min/sqm, PWP > 10 and <18 mmHg, SVR <1450 dyne/sec/cm(-5), DO(2)> 600 ml/min/sqm) or conventional treatment. RESULTS: there were no differences in terms of in-hospital mortality, cardiovascular morbidity, postoperative renal failure or duration of hospital stay between the groups. CONCLUSIONS: in this study perioperative haemodynamic optimisation was not beneficial.

Aged↗

PubMed2000

A new melatonin receptor ligand with mt1-agonist and MT2-antagonist properties.

It has been difficult, so far, to obtain melatonin analogs possessing high selectivity for the respective melatonin receptors, mt1 and MT2. In the present work, we report the synthesis and pharmacological characterization of a new compound N-¿2-[5-(2-hydroxyethoxy)-1H-indol-3-yl)] ethyl¿ acetamide or 5-hydroxyethoxy-N-acetyltryptamine (5-HEAT). To assess the activity of the compound, the following tests were performed: affinity determination for the high- and low-affinity receptor states (2-[125I]iodomelatonin binding), potency and intrinsic activity in inducing G protein activation ([35S]GTPgammaS binding assay). 5-HEAT showed little selectivity for the mt1 receptor, with pKi values of 7.77 for mt1 and 7.12 for the MT2 receptors, respectively. 5-HEAT was able to differentiate between the high- and the low-affinity receptor states in the mt1 but not in the MT2 receptor. 5-HEAT induced a high level of G protein activation when acting through the mt1 receptor, with a relative intrinsic activity of 0.92. On the contrary, it elicited only minimal MT2 receptor-mediated G protein activation, with a relative intrinsic activity of 0.16, and was also able to inhibit the melatonin-induced MT2 receptor-mediated G protein activation, with a pKB value of 7.4. In conclusion, it appears that 5-HEAT possesses very different efficacies at the two melatonin receptors, behaving as a full melatonin receptor agonist at the mt1 and as an antagonist/weak partial agonist at the MT2 receptor. Therefore, it is a promising ligand for use in functional studies aimed at distinguishing between the effects mediated by the different melatonin receptors in the human.

3T3 Cells↗

PubMed2000

An uncommon cause of pericardial actinomycosis.

Cardiac actinomycosis is rare; the pericardium is the most frequently involved site, but myocardial, endocardial and valvular involvement have all been documented. Most cases originate from a thoracopulmonary site of actinomycosis and spread directly to the pericardium. Widespread dissemination from extrathoracic organs is uncommon; in fact actinomycosis is prevented by anatomical barriers and hematogenous diffusion is rare. We describe an uncommon case of pericardial actinomycosis due to a draining fistula from the liver to the pericardial space across the diaphragm. The massive dissemination through the fistula could explain the peculiar echocardiographic images of macroscopic, echo-reflective, irregular masses, floating in the pericardial space, probably consistent with aggregates of sulfur granules.

Actinomycosis↗

PubMed1998

Melatonin involvement in immunity and cancer

The most studied endocrine product of the pineal gland, melatonin, has been reported to be involved in the feedback between neuroendocrine and immune functions and to exert oncostatic action, at least in certain experimental conditions. Melatonin seems to be an integral part of the immune system, by exerting direct and/or indirect stimulatory effects on both cellular and humoral immunity. Likewise, an antitumor activity of melatonin has been shown in several experimental models in vivo and in vitro. The means by which melatonin exerts its effects on immunity and neoplastic growth have not been elucidated. The different putative mechanisms of action of melatonin investigated so far are here briefly discussed.

Journal Article↗

PubMed1997

1-(2-Alkanamidoethyl)-6-methoxyindole derivatives: a new class of potent indole melatonin analogues.

A new series of indole melatonin analogues, bearing the amido ethyl side chain attached at the N-1 position of the indole nucleus, were synthesized and tested for their affinity for the melatonin receptor isolated from quail optic tecta in a series of in vitro ligand-binding experiments using 2-[125I]iodomelatonin as the labeled ligand. The biological activity was evaluated using two models: effects on the forskolin-stimulated cAMP accumulation in explants from quail optic tecta and evaluation of the GTP gamma S index derived from competition experiments performed in the absence or presence of GTP gamma S. Compounds 2a and 2k-n, obtained by shifting the methoxy group and the ethylamido side chain from the C-5 and C-3 positions of melatonin to the C-6 and N-1 positions of the indole nucleus, exhibited an affinity similar to that of melatonin itself, as well as full agonist activity. Optimization of the C-2 substituent by introducing Br, phenyl, or COOCH3 (2b-d) resulted in a significantly enhanced affinity (in the picomolar range) and improved agonist biological activity. Compounds lacking the methoxy group and bearing an N-alicyclic group (2h-j) behaved as partial agonists or antagonists.

Animals↗

PubMed1995

Modulation of cancer endocrine therapy by melatonin: a phase II study of tamoxifen plus melatonin in metastatic breast cancer patients progressing under tamoxifen alone.

Recent observations have shown that the pineal hormone melatonin (MLT) may modulate oestrogen receptor (ER) expression and inhibit breast cancer cell growth. On this basis, we have evaluated the biological and clinical effects of a concomitant MLT therapy in women with metastatic breast cancer who had progressed in response to tamoxifen (TMX) alone. The study included 14 patients with metastasis who did not respond (n = 3) to therapy with TMX alone or progressed after initial stable disease (SD) (n = 11). MLT was given orally at 20 mg day-1 in the evening, every day starting 7 days before TMX, which was given orally at 20 mg day-1 at noon. A partial response was achieved in 4/14 (28.5%) patients (median duration 8 months). The treatment was well tolerated in all cases, and no MLT-induced enhancement of TMX toxicity was seen; on the contrary, most patients experienced a relief of anxiety. Mean serum levels of insulin-like growth factor 1 (IGF-1), which is a growth factor for breast cancer, significantly decreased on therapy, and this decline was significantly higher in responders than in patients with SD or progression. This pilot phase II study would suggest that the concomitant administration of the pineal hormone MLT may induce objective tumour regressions in metastatic breast cancer patients refractory to TMX alone.

Adult↗

PubMed1995

Dobutamine echocardiography: usefulness of digital image processing.

The present study was undertaken in order specifically to evaluate the usefulness of digital image processing so as to enhance the diagnostic power of dobutamine stress echocardiography. For this purpose 44 dobutamine echocardiographic tests, routinely performed in our echo laboratory, were analysed blindly by two observers using traditional videotape recording and digitized image acquisition. The results obtained from both observers show a trend which suggests that the traditional videotape approach provides more true-positive tests than the digitized approach (27/38 vs 23/38 and 24/38 vs 22/38 for the first and second observer, respectively). True-negative test detection was 6/6 with the videotape and 5/6 with the digitized method for both observers. As a consequence of the discrepancies observed between the two modalities, the videotape indicates that it can provide higher diagnostic accuracy than the digitized approach (72 +/- 9% vs 63 +/- 10%). The tests results concordance (positive or negative) between the two modalities of analysis was 66% for both the observers. The inter-observer agreement on the test results was 84% and 80% for the videotape analysis and the digitized analysis, respectively. On the basis of the results, we consider that digitized analysis applied to dobutamine stress echocardiography does not afford significant diagnostic advantages and should not be considered as an alternative option to traditional videotape analysis. However, it may be considered an extremely useful integrative tool since it produces the on-line image evaluation more easily and faster and allows a more practical form of stress test storage.

Adult↗

PubMed1994

Modulation of melatonin secretion by acetyl-L-carnitine in adult and old rats.

Modification of melatonin synthesis and release by acetyl-L-carnitine (ALC) was studied in adult (2 month old) and old (24-month-old) male Sprague Dawley rats. When ALC was injected at 1500 into adult rats at doses of 10, 30, or 90 mg/kg, there was a remarkable increase in their pineal and serum melatonin 1 hr later. However, using the same experimental protocol acute ALC administration in old rats did not modify pineal and serum melatonin levels. ALC administered in the same dose range induced a significant increase in pineal and serum melatonin in adult rats treated at 0100 h following exposure of 30 min to bright, white light to suppress endogenous melatonin. In the same conditions, in old rats, only the higher dose (90 mg/kg) caused any noteworthy increase in melatonin pineal content while lower doses were uneffective both on serum and pineal melatonin levels. It is known that ALC affects fatty acid transport in the cells, modulates CoA, modifies neuronal transmission and reduces lipofuscin accumulation which is related to lipid peroxidation. The action of ALC on melatonin synthesis could be the result of a modulation of the neuronal transmission related to circadian pineal endocrine activity. Moreover, since both ALC and melatonin exert remarkable scavenger activity, it is possible to suppose that ALC effects in reversing certain aging processing may be due to its ability to promote melatonin production.

Acetylcarnitine↗

PubMed1993

Hemodynamic effects of nifedipine in patients with asymptomatic aortic regurgitation: evaluation by Doppler echocardiography.

Nineteen asymptomatic patients affected by isolated chronic aortic regurgitation received 20 mg of nifedipine sublingually: the acute hemodynamic effects of nifedipine were evaluated by combined cross-sectional and Doppler echocardiography. To assess variations in the regurgitant flow volume, the flow volume across the mitral and aortic valves was calculated as the product of velocity-time integral multiplied by the orifice valve area. Flow volume across these valves represented the total stroke volume, and forward stroke volume, respectively: the regurgitant volume was obtained by calculating the difference between total and forward stroke volume. Nifedipine induced a redistribution of the two components of the total left ventricular stroke volume: regurgitant stroke volume decreased from 57 +/- 22 ml/beat to 46 +/- 21 ml/beat (P < 0.002), while forward stroke volume increased from 83 +/- 12 to 93 +/- 15 ml/beat (P < 0.0005), as a consequence of the reduction in systemic vascular resistance from 1513 +/- 378 to 1092 +/- 307 dynes.sec.cm-5 (P < 0.0001). The reduction of regurgitant volume was due to either a 24.8% decrease of the aortic-left ventricular mean pressure gradient during diastole (P < 0.008) or a 6% decrease of the diastolic time interval (P < 0.04). The effect of these acute changes on left ventricular loading was to induce a reduction in oxygen consumption which was expressed by a decrease in the double product (from 10176 +/- 1767 to 9444 +/- 1559 mmHg.beats/min; P < 0.002), in spite of a significant increase in heart rate. This study, therefore, shows the beneficial acute hemodynamic effect induced by nifedipine in asymptomatic patients affected by chronic aortic regurgitation and shows that Doppler-echocardiography is a useful instrument for the evaluation of hemodynamic changes immediately after the administration of drugs.

Administration, Sublingual↗

PubMed1993

[Myocardial response to ischemia produced by repeated coronary occlusions: an experimental study].

BACKGROUND: The fact that brief repeated episodes of ischemia may induce prolonged functional depression of the left ventricle is still a matter of debate. During an angioplasty several brief (20-90 sec) coronary occlusions are performed, with the potential risk of inducing myocardial jeopardy. METHODS: We performed 4 repeated LAD occlusions in 7 open chest pigs under general anesthesia and controlled ventilation. The following parameters were evaluated: mean systemic arterial pressure (MAP), left ventricular peak systolic pressure (LVPSP), heart rate (HR), and peak negative and positive dP/dt (dP/dt- and +). Each parameter was measured in the basal state and every 4 sec, in the expiratory phase, during the coronary occlusion, the first min and after 10 min of reperfusion. The percent change from control values for each parameter was also calculated and, by means of the ANOVA test, the differences among the 4 consecutive occlusions for each parameter were tested. RESULTS: The results showed that: 1) coronary occlusions significantly depressed dP/dt + and -, MAP and LVPSP, while HR did not change; 2) each variable returned to control values within 1 min of reperfusion; 3) the response to ischemia (percent change) was the same in each of the 4 consecutive occlusions for all parameters at every recording time. CONCLUSIONS: We can conclude that: 1) each experimental coronary occlusion induces a depression of myocardial function that is reversible in 1 min of reperfusion; 2) four repeated 2 minutes coronary occlusions do not induce cumulative effects on myocardial response to ischemia.

Analysis of Variance↗

PubMed1991

In vivo and in vitro studies on modulation of the pineal endocrine function by L-acetyl-carnitine in the rat.

Male Sprague-Dawley rats injected (i.p.) at 1500h with L-acetyl-carnitine in doses of 10, 30 or 90 mg/kg exhibited a notable increase in their pineal and serum melatonin content 1 hr later. Likewise, L-acetyl-carnitine administered in the same dose range induced a significant increase of pineal and serum melatonin content in rats treated at 0100h, following exposure of 30 min to bright white light to suppress endogenous melatonin. Under in vitro experimental conditions, however, 60 min of coincubation of isolated rat pineal glands with L-acetyl-carnitine (10(-5) M) did not result in an elevation in melatonin accumulated in the incubation medium. These results demonstrate that, in vivo, L-acetyl-carnitine can exert a modulatory action on synthesis and release of melatonin, possibly by modifying noradrenergic transmission and signal transduction in the pineal gland.

Acetylcarnitine↗

PubMed1991

Clinical results with the pineal hormone melatonin in advanced cancer resistant to standard antitumor therapies.

The pineal hormone melatonin (MLT) is able to exert an oncostatic action. Its possible use in the treatment of human tumors, however, has not yet been investigated. The present study was carried out to evaluate the effects of MLT in patients with metastatic solid tumors resistant to conventional therapies. The study included 54 patients, most of them were affected by lung cancer or colorectal carcinoma. MLT was given intramuscularly at a daily dose of 20 mg at 3.00 p.m. for 2 months; this induction phase was followed by a maintenance period at a dose of 10 mg orally in responder patients or in those with an improvement in performance status (PS). The clinical response was as follows: 1 partial response (cancer of pancreas), 2 minor responses (colon cancer and hepatocarcinoma) and 21 with stable disease. The remaining 30 patients rapidly progressed within the first 2 months of therapy. An evident improvement in PS was achieved in 18 of 54 (33%) cases. These results, by showing an apparent control of the neoplastic growth and an improvement in the quality of life in a reasonable number of cancer patients for whom no other standard therapy is available, would justify further clinical trials to better define the impact of MLT therapy on the survival and quality of life of untreatable advanced cancer patients.

Adult↗

PubMed1990

[Effects of low-dose diltiazem on isovolumetric relaxation and contraction].

Calcium entry blockers are commonly believed to have a direct negative inotropic effect, but systolic function of the left ventricle (LV) can be improved when the peripheral vasodilator activity of the drug is present. The aim of our study was to evaluate the effect of diltiazem (D) on isovolumic contraction (IC) and relaxation (IR) at a dosage which is not effective on the peripheral vascular bed. We infused 10 micrograms/Kg/min i.v. of D for a 30 min period in to 12 pigs, anesthetized with ethyl urethane (1250 mg/Kg) and under artificial ventilation. The following variables were evaluated: left ventricular systolic (LVSP) and end-diastolic (LVEDP) pressure, peak - and + dP/dt, mean arterial pressure (MAP), heart rate (HR) and double product. The recordings were obtained in the control condition and 5, 10, 15, 20, 25 and 30 minutes after beginning the infusion. The statistical analysis was performed using the one-way ANOVA test. Our results show: 1) a maximal increase in the peak + dP/dt from 2228 +/- 501 to 2448 +/- 576 mmHg/sec (p less than or equal to 0.01) and of the peak . dP/dt from 1262 +/- 260 to 1348 +/- 272 mmHg/sec (p less than or equal to 0.05); 2) and increase in LVSP from 86 +/- 13 to 90 +/- 10 mmHg (p less than or equal to 0.01) and 3) no changes in HR, PAM, LVEDP and double product. As the indices representing afterload and preload (PAM and LVEDP) remained unchanged during the infusion, we suggest that the increase in dP/dt + and - are due to a direct effect of diltiazem on myocardial function.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed1988

A study on the relationship between the pineal gland and the opioid system in patients with cancer. Preliminary considerations.

Recent studies showed that both the pineal gland and the endogenous opioid system are involved in the modulation of the immune system and in the regulation of tumor growth. Moreover, a relationship between pineal and opioid system has been demonstrated. In order get an overall view of the psychoneuroendocrine interactions in cancer patients, the levels of melatonin, the most important pineal hormone, and of beta-endorphin have been measured on blood samples collected during the morning. The study was carried out on 54 patients, 42 healthy subjects, and in 34 patients having illnesses other than cancer. Breast cancer, lung carcinoma, and colorectum cancer were the three neoplasms detected in the patients investigated. Growth hormone (GH), somatomedin-C and prolactin (PRL) levels were also determined. beta-endorphin levels were found to be substantially within the normal range in patients with cancer, whereas those of melatonin were raised in several cases. The beta-endorphin/melatonin ratio was higher than 2 in normal subjects, in non-neoplastic patients and in most cancer patients without metastases, whereas this ratio was lower than 2 in almost all patients in a metastatic stage of the disease. Neither melatonin levels nor those of beta-endorphin appeared to be significantly correlated with GH, somatomedin-C, and PRL concentrations. The low beta-endorphin/melatonin ratio observed in metastatic patients suggests the presence of an unbalanced relation between the pineal and the opioid system in those subjects. Therefore, an anomalous relationship between pineal function and opioid activity might play a role in the clinical course of neoplastic disease.

Adult↗

PubMed1988

Alteration of opioid peptide circadian rhythm in cancer patients.

Endogenous opioid peptides have been seen to play a role in regulating immunity and tumor growth. This study was carried out to investigate opioid activity in human cancer. We evaluated by radioimmunoassay beta-endorphin plasma levels on blood samples collected at 9.00 a.m. from 121 cancer patients and 42 healthy subjects. In 22 cancer patients and in 12 controls, beta-endorphin circadian rhythm was also investigated. Finally, in 14 cancer patients and in 10 controls GH, PRL, FSH, LH and cortisol serum levels were measured after the administration of a metenkephalin analogue, FK 33-824 (0.3 mg i.v.). No significant differences were seen in beta-endorphin mean levels between cancer patients and normal subjects. Moreover, no differences were found between patients with or without metastases, nor between those with or without chronic pain. beta-Endorphin circadian rhythm appeared to be altered in 16/22 cancer patients, and anomalous hormonal responses to FK 33-824 were seen in 13/14 patients. This study shows an altered opioid activity in human neoplasms, whose clinical significance remains to be determined.

Adult↗

PubMed1988

The pineal gland-opioid system relation: melatonin-naloxone interactions in regulating GH and LH releases in man.

Several observations have demonstrated that the opioid system can modulate melatonin secretion from the pineal gland and that the effects of opioids may require a pineal participation. In contrast, the role played by the pineal gland in regulating the synthesis and secretion of endorphins and enkephalins in still obscure. To establish whether the neuroendocrine activity of melatonin are mediated by endogenous opioids and to demonstrate a possible action exerted by the pineal gland on opioid peptides, GH and LH serum mean levels were evaluated by RIA in 12 healthy subjects of both sexes after melatonin injection alone (0.4 mg/kg bw im at 09:00 h) and on a separate occasion after a simultaneous administration of melatonin and naloxone (1.2 mg iv as a bolus, followed by an iv infusion of 1.6 mg/h for 3h). On an other occasion, the study was performed during saline or naloxone infusion alone. In each test, venous blood samples were collected at -20, 0, 30, 60, 90, 120 and 180 min. A significant rise of GH was observed after melatonin injection alone. The simultaneous infusion of naloxone blocked melatonin-induced GH rise. Melatonin did not affected LH serum levels, while it was able to reduce LH increase induced by naloxone. These preliminary results suggest that some neuroendocrine effects of melatonin might be mediated by a modulation on the opioid tone.

Adult↗

PubMed1988

Action of morphine on melatonin release in the rat.

Some data from the literature raised the possibility of an interaction between the opioidergic system and pineal secretion. The present study was undertaken in order to investigate the acute influence exerted by opioids upon plasma melatonin levels in the albino rat. Different doses of morphine hydrochloride were injected (1, 1.5, 2, 3 mg/kg) intraperitoneally into anaesthetized adult male rats bearing a cannula previously inserted into the carotid. Blood samples were collected subsequently at 30-min intervals, within a period of 90 min following drug administration. Plasma melatonin contents were determined by a radioimmunoassay (RIA) method. Acute administration resulted in a dose-dependent increase in plasma melatonin concentration when compared to the respective controls. This effect is blocked by pretreatment with Naloxone. The present result seem to support the hypothesis that the opioidergic system, in certain circumstances, might contribute to the activation of melatonin secretion.

Animals↗