Search PubMed⌕ Search

Biomedical subjects

A Longo

Publications and source records attributed to A Longo.

At least 91 records · Page 5Linked to original sources
PubMed1989

5-Aza-2'-deoxycytidine as inducer of differentiation and growth inhibition in mouse neuroblastoma cells.

We studied the effect of 5-aza-2'-deoxycytidine (5-AZA-CdR) on the differentiation of murine 41A3 neuroblastoma cells. Neuroblastoma cells treated with 0.1-1.0 microM 5-AZA-CdR underwent differentiation; markers of neuronal functions, such as acetylcholinesterase activity and growth of nerve fibers, were expressed at a higher level in the drug-treated cells than in the controls. This increased expression was accompanied by significant hypomethylation of newly synthesized DNA. A secondary event seemed to be a partial inhibition of DNA synthesis, cell proliferation and colony-forming activity. These effects were more pronounced than those caused by the related cytidine analog, 1-beta-D-arabinosil-cytosine (ARA-C). The results obtained suggest that 5-AZA-CdR may be an effective agent for the growth control of human neuroblastoma cells.

Acetylcholinesterase↗
PubMed1989

Neuropsychological results of long-term therapy with oxiracetam in patients with dementia of Alzheimer type and multi-infarct dementia in comparison with a control group.

The cognitive and behavioral effects of oxiracetam therapy during long-term treatment in patients with dementia of Alzheimer type (DAT) and multi-infarct dementia (MID) were studied in comparison with a historical control group. Twenty DAT/MID outpatients, aged 54-86 years, received oxiracetam (800 mg twice a day) for a period of 6 months. Another 20 DAT/MID outpatients, aged 67-85 years, were selected from our clinical records in order to obtain a control group of patients matched for age, sex, diagnosis, baseline Mini Mental State Examination (MMSE) score and follow-up duration. All the patients were diagnosed as having mild to moderate degrees of dementia as defined by a baseline MMSE score between 14 and 24. The patients of both groups underwent, both at baseline and after 6 months, the following neuropsychological tests: MMSE, Idiopathic Cerebral Dysfunction Scale, Babcock Test, Gibson Spiral, Toulouse-Pieron Test. Statistical analysis of experimental data demonstrated that at baseline the two groups were comparable. At the end of the study period the oxiracetam group scored significantly better on the majority of the tests evaluating memory, attention, orientation, concentration and psychomotricity than the control group, in which a worsening trend was seen on the whole. No side effects were seen during oxiracetam treatment. The present study, showing positive clinical findings after long-term oxiracetam therapy in controlled conditions, confirms that this drug can be a useful pharmacological treatment for mild to moderate degrees of dementia.

Aged↗
PubMed1989

Epidermal growth factor receptors in human hyperplastic prostate tissue and their modulation by chronic treatment with a gonadotropin-releasing hormone analog.

We characterized the epidermal growth factor (EGF) receptor in the membrane fraction of prostatic tissue from men with benign prostatic hyperplasia (BPH). The maximum specific binding of [125I]EGF to the BPH membrane fraction was achieved after 30-min incubation at 35 C. Analysis of the binding data revealed two classes of binding sites, one of high affinity [Kd, 2.5 +/- 0.5 (+/- SE) x 10(-11) mol/L] and one of lower affinity (2.2 +/- 0.3 x 10(-9) mol/L). [125I]EGF binding was inhibited by excess EGF, but not by insulin, proinsulin, fibroblast growth factor, or insulin-like growth factors I and II. In prostatic tissue of men with BPH treated for 3 months with the GnRH agonist analog Goserelin (Zoladex, depot formulation), the binding capacities of both sites were significantly higher than those of BPH tissue from untreated men (P less than 0.001). These results demonstrate that prostatic tissue from men with BPH contains two classes of specific binding sites for EGF, and their levels are modulated by chronic GnRH agonists treatment.

Aged↗
PubMed1989

[Holter ECG in evaluating myocardial ischemia. Validation using the exercise test].

OBJECTIVES: Validation of ST-T ischemic changes in the Holter system by those recorded in the 12-lead ECG during the exercise test. DESIGN: The changes induced by the exercise test in the ST segment of the two Holter leads--aVF e V5 like--were compared with the changes simultaneously registered in the 12-lead ECG. SETTING: Exercise Test Laboratory and Holter Laboratory of the UTIC-Arsénio Cordeiro. Hospital de Santa Maria de Lisboa. PATIENTS: 31 patients, 23 male and 8 female, with a mean age of 55 +/- 7 years, 84% with ischemic heart disease. METHODS: The patients underwent a treadmill exercise test. 28 with the Bruce protocol and 3 with the Naugton protocol, during which the electrocardiogram was registered simultaneously with a 2-channel Holter recorder and by a conventional 12-lead system. The changes induced in the ST segment in the two systems were compared. RESULTS: The results of the two tests were concordant in 94% of the patients. In 4 patients (13%) there was not a good correlation between the inferior and anterior leads of the two methods, which diverged mainly between the Holter lead aVF and the inferior leads of the conventional ECG. The morphology of the ST depression was similar in both methods, and the severity of ST depression as judged by its amplitude showed an excellent positive linear correlation (r = 0.8542, p less than 0.001). CONCLUSIONS: The sensitivity and the specificity of the Holter system is similar to the conventional 12-lead ECG in detecting ischemic changes during exercise whenever they have electrocardiographic evidence.

Adult↗
PubMed1989

[Comparison of Holter electrocardiography and thallium 201 scintigraphy in the detection of myocardial ischemia].

OBJECTIVE OF THE STUDY: To compare ischemic changes (I) detected by Holter ECG (H ECG) to the myocardial perfusion defects found in 201 TI myocardial perfusion scintigraphy. DESIGN: 201 TI exercise test was made during the performance of a 24 hours H ECG. The validation of ST segment changes detected by H ECG during the exercise test was made on basis of reversible myocardial perfusion defects (RPD) detected on 201 TL and a relation between ST segment changes detected during the remaining 24 hours recording period and 201 TI (TI) RPD was established. SETTING: The patients (pt) included in the study have come from Cardiology and Heart Surgery Clinics of a Central teaching hospital. MATERIAL AND METHODS: 20 pt with a high coronary artery disease prevalence have been submitted to a two lead (V5 and aVF) 24 hour H ECG during which they have performed a symptom limited bicycle exercise test followed by an injection of 201 TI with acquisition 5 minutes later. Ischemic episodes detected on H ECG were quantified and their relation with heart rate and symptoms was established. As far as 201 TI studies are concerned the fixed and reversible perfusion defects as well as their location were evaluated. RESULTS: 1. H ECG: 6 pt (30%) presented ST changes on H ECG during the exercise test and a total of 9 pt (45%) had ST changes during exercise and during the remaining period of H ECG. 2. TI: 19 pt presented perfusion defects images (fixed in 7, reversible in 14, both kinds of defects in 7). 3. H ECG validation: H ECG during exercise presented I in 6 out of 14 pt with RPD on TI (sensitivity = 43%). Six of these 8 pt, with negative H and positive TI, had a chronic myocardial infarction. All the 6 pt with negative TI had negative H ECG (specificity = 100%). 4. H ECG TI comparison: 7 (50%) of the 14 pt with RPD had ST changes on 24 hrs H ECG. Seven of 11 pt with negative H ECG had RPD in TI. Two pt with negative TI had positive H ECG. These 2 pt had during H ECG a higher heart rate (HR) than the HR recorded during the exercise test. CONCLUSIONS: 1. In pt with known CAD, TI has a high sensitivity and specificity to show perfusion defects. 2. Considering TI as gold standard, H ECG showed to be a useful method to detect I in the studied population (sens. = 43%; spec. = 100%). 3. H ECG revealed to be an important diagnostic tool in detecting additional I episodes beyond the ones recorded during TI exercise test.

Adult↗
PubMed1989

Pharmacokinetics and bioavailability of oral acetylcysteine in healthy volunteers.

The plasma pharmacokinetics of oral acetylcysteine(N-acetylcysteine, NAC) after the administration of single 600 mg and repeated 200 mg doses and the relative bioavailability of the two regimens were studied in 12 adult subjects. On two different occasions in a cross-over, balanced fashion the subjects were administered orally either a single dose of NAC 600 mg as effervescent tablets or 4 repeated doses of NAC as granules in sachets at the regimen of 200 mg t.i.d. Venous blood samples were obtained just before dosing and 20, 40 min, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 h after the administration of NAC 600 mg; with the 1st, the 2nd and the 4th doses of NAC 200 mg samples were taken just before dosing and after 20, 40 min, 1, 1.5, 2, 3, 4, 6 and 8 h, the last sampling after the 1st dose being the one before the 2nd dose. A detailed description of the assaying methods of NAC is given in the text. As indexes of bioavailability Cmax' tmax and AUC of NAC plasma concentrations were considered and MRT was taken as an estimate of its persistence in plasma. NAC was quickly absorbed without any significant difference in tmax among the doses. With the 600 mg dose Cmax' AUC and MRT were greater than with a single 200 mg dose; after summing up the values of these parameters for the 200 mg doses no significant differences were observed in comparison to the single 600 mg dose in Cmax and AUC, while MRT resulted significantly higher.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcysteine↗
PubMed1989

Relative bioavailability of fosfomycin and of trometamol after administration of single dose by oral route of fosfomycin trometamol in fasting conditions and after a meal.

The pharmacokinetics of fosfomycin and trometamol after single oral dose of fosfomycin trometamol (Z 1282) was studied in healthy volunteers in fasting conditions and immediately after standard meal. The dose was of 1.876 g (equivalent to 1.0 g of fosfomycin). The parameters considered were: serum apparent elimination half-life (t1/2), maximum serum concentration (Cmax), time to Cmax (tmax), area under the curve of the serum concentrations from time 0 (zero) to infinity (AUC0-infinity) and urinary recovery in the first 48 h. The results confirm that fosfomycin trometamol allows high bioavailability of fosfomycin. The absorption and elimination rates of fosfomycin and trometamol in the serum were similar. A statistically significant difference was found between the Cmax values of fosfomycin in the 2 experimental conditions. Means +/- SE of Cmax (micrograms/ml) were 12.1 +/- 0.6 in fasting conditions and 7.8 +/- 1.6 after a meal. Urinary recovery of the antibiotic was high in both experimental conditions. The fraction of the dose recovered (the dose being taken as equal to 1) was on the average 0.58 in the first condition and 0.52 in the second. Urinary recoveries of trometamol in the 2 different conditions were similar.

Administration, Oral↗
PubMed1988

Ibopamine kinetics after single and multiple dosing in patients with congestive heart failure.

The pharmacokinetics of ibopamine after single and multiple dosing was studied in 20 patients with congestive heart failure (CHF) of NYHA functional class II. Ibopamine 100 mg was given 3 times a day for 7 days in 6 patients and for 30 days in the other 14 patients. Plasma pharmacokinetics of total (mainly conjugated) and free epinine was studied after the first dose and on the 3rd, 7th and 30th days of treatment. The urinary recoveries of total epinine, HVA and DOPAC were measured in 5 patients for 24 h after ibopamine ingestion on the 1st and 30th days. Plasma pharmacokinetics of ibopamine did not vary during the repeated administration of the drug. In the course of the treatment, total epinine elimination t1/2 showed no significant variations. The build-up of Cmax, Cmin and AUC of total epinine observed after multiple dosing was as expected on the basis of the interval adopted between the doses of ibopamine and of the elimination t1/2 of total epinine. Pharmacokinetic parameters of free epinine did not show significant variations during the course of the treatment. The amounts of HVA and DOPAC recovered in urine on the 1st and 30th days of treatment were similar while the amount of total epinine was greater on the 30th day, the increment mainly reflecting a partial carry over of the less rapidly excreted conjugated epinine from the last previous doses. The results obtained for free epinine plasma levels and for the urinary recoveries of ibopamine metabolites thus indicated that no saturation of the enzymes involved in ibopamine metabolism occurred.

Aged↗
PubMed1988

Ibopamine kinetics after a single oral dose in patients with congestive heart failure.

The kinetics of ibopamine, the 3,4-diisobutyryl ester of N-methyldopamine (epinine), was assessed in 27 patients with congestive heart failure (CHF) and 8 healthy normal subjects (NS). Nine patients were in functional class IV according to the NYHA definition, 9 in class III and 9 in class II. Ibopamine was administered at a single oral dose of 100 mg. Epinine, both free and total (mainly conjugated), plasma concentrations and urinary recoveries of total epinine, HVA and DOPAC were studied. The results showed that ibopamine kinetics is not substantially different in CHF patients and in NS. In both groups the absorption of the drug was equally prompt and elevated. Mean Cmax, tmax and AUC infinity values of total epinine in CHF patients did not differ significantly from those in NS. In CHF patients t 1/2 of total epinine was significantly higher than in NS (4.1 +/- 0.2 h vs 3.1 +/- 0.2 h, mean +/- SE). Mean Cmax, tmax, AUCt and MRT values of free epinine in CHF patients were not significantly different from those in NS. The urinary recovery of the 3 metabolites considered together was comparable in CHF patients and in NS. The mean +/- SE total urinary recoveries in the 24 h after dosing, expressed as percentages of the administered dose, were 60 +/- 3 in CHF patients and 69 +/- 4 in NS. Conjugated epinine in urine was found to be constituted by 3-O-sulfate (84%) and 4-O-sulfate (16%).

Administration, Oral↗
PubMed1988

Pharmacokinetics of ibopamine in patients with renal impairment.

The pharmacokinetics of a single oral dose of ibopamine 100 mg were studied in 15 patients with various degrees of chronic renal impairment (CRI) and in 8 subjects with normal renal function and of comparable age, taken as a control group. Plasma total (mainly conjugated) and free epinine and urinary metabolites (total epinine, HVA and DOPAC) were measured. Both total and free epinine were detectable at the earliest sampling time (15 min) in CRI patients and in normal subjects, thus confirming the promptness of ibopamine absorption. Free epinine pharmacokinetic parameters did not show any appreciable differences among the groups with different degrees of renal impairment, and no statistically significant differences were observed between normal subjects and CRI patients. Progressive renal impairment was associated with higher Cmax, longer t1/2 and larger AUC infinity of total epinine, and with reduced urinary elimination of total epinine and metabolites. Statistically significant differences (p less than 0.01) in Cmax/70 kg, t1/2, and AUC infinity/70 kg of total epinine were found between normal subjects and patients with mild renal impairment. No statistically significant differences were observed in 24-h urinary recoveries of both total epinine and metabolites between normal subjects and patients with mild renal impairment. No adverse effects were experienced during the course of the study. As the kinetics of ibopamine's active moiety, free epinine, were not apparently altered by chronic renal failure, adjustment of its dosage should not be necessary in renal diseases.

Adolescent↗
PubMed1987

Acetylcholinesterase in neuroblastoma and neuroblastoma x glioma hybrid cells: cellular localization and molecular forms.

The cellular localization of acetylcholinesterase (AChE) was investigated at the electron microscope (E.M.) in a neuroblastoma and neuroblastoma x glioma hybrid line, which differ for their ability to establish synaptic contacts. Only cells of the latter line show association of AChE to the plasmamembrane, while in the former the activity is mainly intracellular. Sucrose sedimentation analysis of AChE molecular forms has shown no significant differences in the distribution of the two forms, G2 and G4, between the two cell lines. On the contrary a marked difference is observed in the ability of the cell to release the enzyme in the culture medium. In fact the cells lacking AChE on their surface release in the medium a much higher proportion of their enzyme, than the cells showing AChE association to their plamamembrane. The possible role of two alternative fates for AChE, secretion or membrane insertion, in determining the observed differences of enzyme localization is discussed.

Acetylcholinesterase↗