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Biomedical subjects

R Latini

Publications and source records attributed to R Latini.

At least 73 records · Page 4Linked to original sources
PubMed1994

On the suitability of urethane bonds between the carrier and the drug moiety in poly(ethyleneglycol)-based oligomeric prodrugs.

Some poly(ethyleneglycol) derivatives of propranolol were prepared, in which the drug molecule was linked to the oligomeric carrier via urethane bonds in order to study the suitability of this bond as a linkage between the carrier and the drug moiety in oligomeric prodrugs. For comparison purposes also ethanol- and butanol-based prodrugs of propranolol were prepared, with the same linkage between drug and promoiety. The urethane compounds were obtained by condensation via N,N'-carbonyldiimidazole. None of these compounds gave rise to appreciable blood concentrations of propranolol after oral administration, thus suggesting in this particular case, a relative in vivo resistance of urethane bonds towards cleavage.

Administration, Oral↗
PubMed1994

Pharmacokinetic results on naproxen prodrugs based on poly(ethyleneglycol)s.

Five prodrugs of S(+)-2-(6-methoxy-2-naphthyl)propionic acid (naproxen), in which the drug was bound by ester linkages to diethyleneglycol (I), triethyleneglycol (II), octanediol (III), butyl-triethyleneglycol (IV), and butyl-tetraethyleneglycol (V), respectively, were prepared and tested for their pharmacokinetic properties after oral administration. It was found that bioavailabilities decreased in the order, and in all cases were lower than that of the free drug.

Administration, Oral↗
PubMed1994

Cytokines in acute myocardial infarction: selective increase in circulating tumor necrosis factor, its soluble receptor, and interleukin-1 receptor antagonist.

Cytokines play a pathogenetic role in a variety of infective and inflammatory diseases. In the present study, we had two objectives: (a) to define the kinetics of tumor necrosis factor (TNF) in plasma after acute myocardial infarction (AMI) in patients treated with early thrombolysis, and (b) to measure other cytokines, interleukin-1 (IL-1) and TNF receptor antagonists, in plasma. TNF-alpha, but not IL-1 beta or IL-8, was present in plasma of 6 of 7 patients with severe AMI (Killip class 3 or 4). No TNF (< 50 pg/ml) was detected in a group of 11 patients with uncomplicated myocardial infarction (Killip class 1) or in control patients without AMI. Soluble TNF receptor type I and IL-1 receptor antagonist (IL-1Ra) were also significantly increased in the group with severe AMI compared with those with uncomplicated AMI. Circulating TNF is increased only in AMI complicated by heart failure at hospital admission. This finding may have diagnostic and therapeutic relevance.

Aged↗
PubMed1993

Influence of diabetes on mortality in acute myocardial infarction: data from the GISSI-2 study.

OBJECTIVES: This study was conducted to determine the role of insulin-dependent and noninsulin-dependent diabetes in the prognosis of patients after myocardial infarction and treatment with fibrinolytic agents. BACKGROUND: Several studies have shown that diabetic patients have a high mortality rate after acute myocardial infarction. However, the impact of diabetes on survival in patients treated with fibrinolytic agents is still undefined. It is also not known whether the type of diabetes or gender affects prognosis. METHODS: We analyzed prevalence and prognostic significance of a history of diabetes in patients enrolled in the GISSI-2 study, all of whom received fibrinolytic agents. The incidence of deaths in the hospital and at 6 months after study entry was computed for patients without diabetes and for insulin-dependent and noninsulin-dependent diabetic patients; relative risks were evaluated by univariate and multivariate analysis. RESULTS: Information on diabetic status was available for 11,667 patients, 94.2% of those randomized in the GISSI-2 study. The prevalence of diabetes was higher in women than in men (8.75% vs. 1.85%, p < 0.01 for insulin-dependent and 23.7% vs. 13.8%, p < 0.01 for noninsulin-dependent diabetic patients). The type of fibrinolytic agent did not affect mortality rates; the increase in in-hospital mortality of diabetic patients was moderate and similar for men with insulin- and noninsulin-dependent diabetes (8.7% and 10.1%, respectively, vs. 5.8% in nondiabetic patients); in women, mortality was markedly higher for insulin-dependent and only slightly higher for noninsulin-dependent diabetic patients (24.0% and 15.8%, respectively, vs. 13.9% for nondiabetic patients). The adjusted relative risks were 1.9 (95% confidence interval 1.2 to 2.9) for insulin-dependent diabetic women and 1.4 (95% confidence interval 1.1 to 1.8) for noninsulin-dependent diabetic men. The mortality rate after discharge showed a similar gender difference, and in insulin-dependent diabetic women, prognosis was ominous even in the absence of left ventricular damage before discharge. CONCLUSIONS: A history of diabetes is associated with a worse prognosis after myocardial infarction, even in patients treated with fibrinolytic agents. Gender and type of diabetes appear to be critical in affecting survival. In men, both insulin-dependent and noninsulin-dependent diabetes are associated with a moderately higher mortality rate; in women, insulin-dependent diabetes is, in itself, a strong risk factor for death after myocardial infarction.

Aged↗
PubMed1993

[The noninvasive quantitative evaluation of the acute hemodynamic effects of sublingual and transdermal nitroglycerin in man].

BACKGROUND: Organic nitrates are complex vasodilators: the hemodynamic action of these drugs is different in the venous and arterial resistance and capacitance beds. The aim of our study was to obtain a quantitative, noninvasive evaluation of the acute effects of sublingual and transdermal (td) nitroglycerin (NTG). METHODS: Twenty-one pts (mean age 49 years) underwent strain-gauge plethysmography and digital photoplethysmography under control conditions, 5 min after sublingual NTG (0.4 mg), 1 hour thereafter and 2 hours after NTG td (10 mg patch). Forearm venous capacitance (CV, ml.100 ml-1) and arteriolar resistance (RA, mmHg.ml-1.100 ml.min) and the b/a ratio of arterial pulse wave (%) were measured. RESULTS: After sublingual NTG, CV increased (+24%, p < 0.01) and b/a was reduced (-35%, p < 0.01), while heart rate and RA increased (+9% and +36% respectively, both p < 0.01). Two hours after NTG td, CV increase was not statistically significant (+11%, p = 0.056), b/a was reduced (-31%, p < 0.01), heart rate and RA did not change. CONCLUSIONS: The combined use of plethysmography and digital photoplethysmography is suitable for the evaluation of vasoactive drugs such as nitrates, which have a complex profile of action on arterial and venous beds. By this method we have shown that NTG td 10 mg dilates venous beds to a low extent; this approach will be utilized in future studies aimed at elucidating dose-response and regimen effect of these drugs.

Administration, Cutaneous↗
PubMed1993

Prolonged cardiopulmonary resuscitation during acute disopyramide poisoning.

A case is reported of sustained electromechanical dissociation due to deliberate disopyramide over-dosage in a young healthy girl. Circulatory recovery was achieved with standard resuscitative measures, including prolonged cardiac massage and isoproterenol infusion plus high dose calcium chloride. Neurological recovery was complete.

Acute Disease↗
PubMed1992

Ventricular arrhythmias and four-year mortality in haemodialysis patients. Gruppo Emodialisi e Patologie Cardiovascolari.

127 randomly selected patients on haemodialysis showed a high prevalence of ventricular arrhythmias, the frequency of which rose significantly during and after dialysis. These patients have now been followed up for 4 years. Only age and ischaemic heart disease correlated independently with mortality. Although ventricular arrhythmias are often associated with cardiac disease in patients on chronic haemodialysis, they do not seem to predict overall mortality.

Arrhythmias, Cardiac↗
PubMed1992

Identification of propafenone metaboliser phenotype from plasma and urine excretion data.

The aim of the study was to validate a test based on analyses of urine to identify the propafenone metaboliser phenotype during routine chronic therapy. Twenty seven patients chronically treated with propafenone were studied. A debrisoquine test was performed in 10. Propafenone and its metabolites in plasma and urine were measured by HPLC. Propafenone, 5-hydroxypropafenone and N-depropylpropafenone concentrations in plasma were 1.09, 0.182 and 0.101 ng.ml-1, respectively. Total recovery of the administered dose in urine was 30.7%. Two patients were identified as PM, based on the result of the debrisoquine test (log D/4OHD of 1.26 and 1.36). This finding was confirmed by the propafenone metabolic ratio in urine, but the plasma data did not permit clearcut separation of the phenotypes. Propafenone/5-hydroxypropafenone in plasma was not a good predictor of metabolizer phenotype. Although the number of patients who completed all three tests was limited, it is concluded that analysis of propafenone/5-hydroxypropafenone in urine collected between two consecutive doses at steady-state is more practical than the debrisoquine test and more specific than determining the propafenone/5-hydroxypropafenone ratio in plasma, for identification of the propafenone metaboliser phenotypes.

Adolescent↗
PubMed1992

Washout of long-term treatment with flecainide and propafenone in patients with complex ventricular arrhythmias and cardiac disease. Antiarrhythmic Drug Evaluation Group.

To assess the spontaneous variability of ventricular arrhythmias after withdrawal of apparently successful antiarrhythmic therapy, we enrolled in a washout protocol 40 patients who had completed a randomized controlled 2-year study of antiarrhythmic drugs (the Antiarrhythmic Drug Evaluation Group [ADEG] study). All of them had heart disease and were first seen with high-grade ventricular arrhythmias (Lown class 4a and 4b) at enrollment. After 2 years all of them had responded to propafenone or flecainide; patients who completed the study on a regimen of amiodarone were not considered for the washout study. A total of 27 patients discontinued flecainide and 13 propafenone. Seven days after withdrawal they underwent 24- or 48-hour ECG testing and were classified as true responders (TR) if the arrhythmias were present at the same level as 2 years previously and false responders (FR) if they were below the ADEG responsiveness level. TR patients had a third 24-hour ECG 7 days later, after rechallenge with the same treatment, and FR patients had a third ECG without drugs. Adherence to the protocol was ascertained by measuring drug plasma concentrations at every 24-hour ECG recording. No differences were found in distribution of heart disease and grade of ventricular arrhythmias between patients in the washout study and the remaining group of the ADEG trial. Twenty-four of 40 patients (60%) were true responders. In 4 of the 17 patients who had a third 24 hour ECG, the responsiveness to the same drug was not confirmed.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗
PubMed1992

Efficacy and safety of short intravenous amiodarone in supraventricular tachyarrhythmias.

The safety and efficacy of short intravenous therapy with amiodarone were evaluated in 44 patients (24 males, 20 females), aged 21-84 years, with supraventricular tachyarrhythmias newly arisen in less than 24 hours. The study group consisted of 15 patients with paroxysmal supraventricular tachycardia, 8 patients with atrial flutter and 21 patients with atrial fibrillation. They were treated with a single infusion of amiodarone up to 2 hours after the restoration of a stable sinus rhythm, or up to a maximum dose of 2400 mg in 24 hours. Our study shows that 88.6% of all supraventricular tachyarrhythmias reverts to sinus rhythm in less than 24 hours: 100% of paroxysmal supraventricular tachycardia, 75% of atrial flutter, and 85.7% of atrial fibrillation. Intravenously administered amiodarone proves to take effect rapidly (0.5 to 22 hours). The plasma amiodarone concentrations at sinus rhythm restoration showed a wide range (405-3800 ng/ml). Piecewise analysis suggested that the probability of sinus rhythm was 14.4-fold greater in paroxysmal supraventricular tachycardia. No linear statistical relationship was detectable between the log-dose-body mass index and log-QTc. Total amiodarone dose and left atrial volume are inversely correlated with a statistically significant difference. The toxicity in our short intravenous course with amiodarone was not relevant. We conclude that short high-dose intravenous amiodarone shows efficacy and safety in all newly occurring supraventricular tachyarrhythmias.

Adult↗
PubMed1992

Effect of lisinopril and isosorbide-5-mononitrate on hemodynamics and mortality in rats with permanent coronary artery occlusion.

We studied the hemodynamic effects of lisinopril and isosorbide-5-mononitrate in rats with permanent coronary occlusion. Rats (n = 35) underwent left coronary occlusion, and ECGs were recorded before and after occlusion. Ventricular arrhythmias were observed in 57% (20 of 35) of animals. Treatment was given immediately after coronary occlusion and for 2 subsequent days. The control group received 100 mg/kg lactose (i.e., 80% vehicle for isosorbide-5-mononitrate). Lisinopril (100 mg/kg body weight) and isosorbide-5-mononitrate (400 mg/kg body weight) reduced systolic blood pressure (SBP) from 134 +/- 9 to 115 +/- 9 mm Hg (p less than 0.05) and from 137 +/- 9 to 126 +/- 9 mm Hg, respectively; the hypotensive effect lasted 2-3 days. No effect on BP was noted in the control group. Overall mortality was 23%; 8 of 35 animals died within 10-15 min of coronary occlusion. Survival after 4 weeks was similar in each group (approximately 80%). Left ventricular pressure (LVP) was measured 4 weeks after coronary artery occlusion and was similar in each group. However, dP/dt was lower in hearts with infarction than in hearts with none (12,608 +/- 906 vs. 8,992 +/- 1,242 mm Hg/s). The extent of the infarction was the same in groups with coronary artery occlusion. Lisinopril is more effective than isosorbide-5-mononitrate in reducing BP after acute myocardial infarction (AMI). Medium-term survival (4 weeks) is not jeopardized by effective treatment with angiotensin-converting enzyme (ACE) inhibitors or long-acting nitrates.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Heart rate variability in patients with ventricular arrhythmias: effect of antiarrhythmic drugs. Antiarrhythmic Drug Evaluation Group (ADEG).

The purpose of this study was to investigate whether heart rate variability could be reliably assessed in patients with ventricular arrhythmias and to evaluate whether it is affected by antiarrhythmic drugs. The study was based on an analysis of 239 ambulatory electrocardiographic (ECG) recordings obtained from 67 patients with frequent and complex ventricular arrhythmias enrolled in the Antiarrhythmic Drug Evaluation Group (ADEG) study. In each recording, after exclusion of premature ventricular complexes, the number of times during a 24 h period in which two consecutive sinus RR intervals differed by more than 50 ms was calculated. The total 24 h count from each recording was then used as an index of heart rate variability. This method is a reliable marker of cardiac parasympathetic activity. Recordings were analyzed at baseline (n = 56), during long-term treatment with amiodarone (n = 17), flecainide (n = 22) or propafenone (n = 17) and after washout in selected patients (n = 5). Despite the presence of a different number of arrhythmias, total 24 h counts in the same patient appeared reproducible over time (r = 0.83 between two different recordings, n = 49, p less than 0.0001). Baseline counts (median 1,698, range 26 to 13,648) were not correlated (r = 0.15) with the number of arrhythmias. The three antiarrhythmic drugs had a disparate effect on total 24 h counts: no change was observed in patients treated with amiodarone (median percent change [delta %]-8, p = NS), whereas a significant (p less than 0.025) decrease occurred in patients treated with flecainide (median delta % -56%) or propafenone (median delta % -64%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

The alpha- and beta-adrenoceptor blocking activities of labetalol and its RR-SR (50:50) stereoisomers.

1. We compared the alpha 1-, alpha 2- and beta 1-adrenoceptor blocking potencies of labetalol with those of its two stereoisomers (RR and SR) in pithed rats and in homogenized rat cerebral cortex and heart. 2. In pithed rats, labetalol and the RR-SR combination were given orally either at doses of 25 and 50 mg kg-1 body wt. or intravenously at doses of 1 and 5 mg kg-1 body wt. Prazosin 4 and 20 micrograms kg-1 body wt. and propranolol 1 and 5 mg kg-1 body wt., were given intravenously for comparison studies of potency at alpha 1- and beta 1-adrenoceptors, respectively. Effects were studied before and after i.v. administration of either phenylephrine (at doses which increased the mean arterial pressure by approximately 80 mmHg) or isoprenaline (at doses that increased heart rate by approximately 100 beats min-1). 3. In pithed rats, labetalol and the RR-SR combination antagonized, in a dose-dependent manner, the pressor effect of phenylephrine (P less than 0.05) and the chronotropic effect of isoprenaline (P less than 0.05). Following both oral and intravenous dosing, the RR-SR combination was twice potent as labetalol in terms of alpha 1- and beta 1-adrenoceptor antagonism at equivalent doses. 4. Labetalol and the enantiomers lacked affinity at alpha 2-adrenoceptors while at alpha 1-adrenoceptors the order of potency was prazosin much greater than RR-SR greater than labetalol. At beta 1-adrenoceptors, the affinity of the compound RR-SR was about 3 times that of labetalol.5. As labetalol is a mixture of active (RR and SR) and inactive (SS and SR) enantiomers (in terms of alpha and beta receptor actions), the combination of RR and SR may be a valuable substitute for labetalol in the treatment of systemic hypertension. Although the potential for non-specific side effects (common to all four enantiomers) could be expected to be diminished, recent reports by postmarketing surveillance indicate that the RR isomer (dilevalol) can induce liver toxicity. Interestingly, labetalol is devoid of this effect; whether the combination of RR and SR enantiomers could be of clinical importance warrants further investigation.

Adrenergic alpha-Antagonists↗
PubMed1991

[Competitive sports activity in subjects undergoing the surgical correction of an ostium-secundum type of interatrial defect: the experience of 9 cases].

Patients who have undergone surgical repair of congenital heart diseases are usually not allowed to participate in competitive sports. In the present study we report our long-term experience with 9 male athletes aged 17 to 23 years who participate in competitive sports after undergoing surgical repair of ostium secundum atrial septal defect at a median age of 9 years; six of them play football and three of them volleyball. Competitive sport activities began 1 to 5 years after surgical repair. The mean duration of follow-up is 88 +/- 26 months. Sport fitness was granted on the basis of the following criteria: 1) a normal physical examination; 2) a normal working capacity on exercise test; 3) no arrhythmias on exercise test and Holter monitoring, recorded also during sport activities; 4) a normal M-mode and two-dimensional echocardiography, including the normalization of right ventricular size; the persistence of an abnormal ventricular septal motion did not exclude sport fitness. Recently we also performed Doppler and color Doppler echocardiography and gated equilibrium radionuclide angiography at rest and during exercise. We studied left ventricular diastolic filling through the pulsed wave Doppler evaluation of transmitral flow and measured cardiac output by continuous wave Doppler echocardiography during exercise test in the supine position. We also performed exercise test and M-mode, two-dimensional, Doppler and color Doppler echocardiography in a control group made up of 15 athletes (10 football players and 5 volleyball players). The exercise duration at graded treadmill exercise test (according to the Carù protocol), the maximal heart rate and the maximal systolic blood pressure were, respectively, 12.9 +/- 0.8 min, 192 +/- 10 beats/min and 198 +/- 12 mmHg. Left ventricular end-diastolic dimension, mass and ejection fraction (single-plane area-length method) were 50.3 +/- 2.8 mm, 210 +/- 38 g and 65 +/- 6%. M-mode right ventricular diastolic dimension was 23.4 +/- 1.6 mm; the right ventricular maximal diastolic diameter and area obtained on two-dimensional echocardiography from the apical four chamber view were 44.1 +/- 3.6 mm and 25 +/- 3.8 cm2 respectively. The evaluation of transmitral flow showed the following data: E velocity 77 +/- 12 cm/sec, A velocity 45 +/- 6 cm/sec, E/A ratio 1.7 +/- 0.3, the isovolumic-relaxation period 72 +/- 8 m/sec and the deceleration half-time of the early rapid filling 71 +/- 10 m/sec. A trivial tricuspid regurgitation was detected in 6 subjects; the peak velocity of the regurgitant jet was less than 2.1 m/sec.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1990

In vivo and perfused liver caffeine kinetics in the rat.

The kinetics of caffeine (1,3,7-TMX) was investigated in male rats given four different doses (1, 2.5, 10 and 25 mg/kg), comparing the patterns found in vivo and after liver perfusion. The same animals were used in both experimental conditions in order to reduce the variability of the caffeine profile. For doses less than 10 mg/kg or mg/L, caffeine blood or perfusate concentrations/time profiles followed first-order kinetics and the elimination rate constant (average 0.013 min-1) and half-life (55 min) were similar for the in vivo and ex vivo conditions. After larger doses (10 and 25 mg/kg or mg/L), kinetics were nonlinear. The area under the blood or medium concentration-time curve increased, but not in proportion to the dose, and modifications of pharmacokinetic parameters were observed, with significant differences for t 1/2 and CL after 10 and 25 mg/kg or mg/L, due to dose-dependent elimination of caffeine at these doses (Km of 8.3 and 7.8 micrograms/ml in vivo and in vitro, respectively). The two different approaches gave close kinetic estimates in vivo and in vitro. Thus, under standardized conditions, the isolated perfused liver technique is a useful tool for studying the kinetics of drugs eliminated by hepatic metabolism.

Animals↗
PubMed1989

Antiinflammatory action of salicylates: aspirin is not a prodrug for salicylate against rat carrageenin pleurisy.

A current hypothesis postulates that the antiinflammatory effect of aspirin (acetylsalicylic acid) is mediated by its metabolite salicylic acid through inhibition of PGE2 synthesis. We tested this hypothesis in rats with carrageenin-induced pleurisy. Aspirin or salicylate, given orally, reduced exudation and cell migration into the pleural cavity, aspirin being more potent than salicylate. The antiinflammatory effect of aspirin cannot be explained only in terms of salicylate formation. Doses of aspirin and salicylate that inhibit inflammation by 50% result in salicylate levels in the exudate of 70 +/- 12 and 323 +/- 17 micrograms/ml, respectively. At a significant antiinflammatory dose (100 mg/kg), salicylate did not reduce the prostaglandin and thromboxane content of the exudate. This indicates that inhibition of cyclooxygenase is not a likely mechanism for the antiinflammatory effect of salicylate. Salicylate only reduced the amount of 6-keto-PGF1 alpha in the exudate at higher doses (200 mg/kg), while aspirin at an equally antiinflammatory dose (50 mg/kg) reduced the content of 6-keto-PGF1 alpha, TXB2, PGD2 but not of PGE2 in the exudate. It therefore seems unlikely that an inhibition of PGE2 synthesis is the common mechanism by which aspirin and salicylate exert their antiinflammatory effects. These results do not supported the hypothesis that aspirin is a prodrug for salicylate but rather indicate that both compounds may exert their antiinflammatory effects partly by different mechanisms.

Animals↗