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Biomedical subjects

E Riva

Publications and source records attributed to E Riva.

At least 181 records · Page 10Linked to original sources

Addison's disease and empty sella.

A 47-year-old woman affected by Addison's disease, inadequately treated with corticosteroids for 14 yr, was referred to our clinic. As a x-ray of skull revealed an enlarged sella turcica, a more thorough study of hypothalamic-pituitary function and of the sellar region was performed. The normal suppression of high plasma ACTH levels induced by hydrocortisone infusion and the normal pattern of ACTH, TSH, PRL, LH and FSH to appropriate stimuli (CRH, TRH, GnRH) excluded the possible existence of an ACTH-secreting adenoma; the CT scan images showed the presence of an empty sella. The impaired GH rise after GHRH may be attributed to either the empty sella or the adrenal failure. This is the first patient with Addison's disease and empty sella, in whom the hypothalamic-pituitary function has been studied by the administration of four releasing hormones.

Addison Disease↗

A40926 aglycone and pseudoaglycones: preparation and biological activity.

A40926 antibiotics are new glycopeptides which are much more active than other members of this class against Neisseria gonorrhoeae. Their activity against Gram-positive bacteria, including coagulase-negative Staphylococci, is similar to that of other glycopeptides. An A40926 preparation containing factors A and B ("A40926 A + B complex") was hydrolyzed to the aglycone and to the mannosyl and N-acylaminoglucuronyl aglycones. The mannosyl aglycone and the aglycone were less active than A40926 A + B complex against Streptococci and Gram-positive anaerobes and lost the anti-gonorrheal activity. In contrast, the N-acylaminoglucuronyl aglycones were as active as the parent complex against these Gram-positive bacteria and were moderately active against N. gonorrhoeae. The aglycone and, even more so, the N-acylaminoglucuronyl aglycones, had better activity than the parent complex against coagulase-negative Staphylococci. In experimental septicemia in the mouse, A40926 A + B complex and its derivatives had activity proportional to their MIC for the test organism.

Animals↗

Determination of teicoplanin in human plasma and urine by affinity and reversed-phase high-performance liquid chromatography.

A sensitive, highly selective and simple high-performance liquid chromatographic method for the determination of teicoplanin, a novel glycopeptide antibiotic, composed of six components, in human plasma and urine is described. After an isolation step by affinity chromatography, the antibiotic substances were chromatographed on a Nucleosil C18 column with phosphate buffer-acetonitrile according to a gradient profile. All the components were detected by their UV absorption at 240 nm. The concentration of teicoplanin was determined by using the external standard procedure. This method was applied to the sum of the six major components as well as to each of them separately. The linearity of the method was checked between 0.5 and 50 micrograms/ml for plasma and between 2 and 50 micrograms/ml for urine. The limit of detection was 0.1 microgram/ml for both biological fluids. The coefficients of variation of the between-day assays did not exceed 8.6 and 8.9% in plasma and urine, respectively. The application of the method to a pharmacokinetic study of teicoplanin after a single intravenous therapeutic dose in a patient is reported. This rapid technique also appears to be suitable for drug monitoring.

Anti-Bacterial Agents↗

Amiodarone induced phospholipidosis. Biochemical, morphological and functional changes in the lungs of rats chronically treated with amiodarone.

Amiodarone, an antiarrhythmic drug, causes pulmonary fibrosis in some patients during chronic treatment but the mechanism is unknown. We studied the effects of amiodarone on pulmonary biochemistry, morphology and function at doses of 25 and 50 mg/kg/12 hr given to rats by gavage for four weeks. Plasma and pulmonary phospholipids were significantly augmented, 13% and 88% respectively, in the group given amiodarone 50 mg/kg/12 hr compared to pair-fed controls. Typical phospholipidosis-like light and electron microscopic alterations were seen in the lung, their severity related to the extent of biochemical changes induced by amiodarone. Pulmonary function tests revealed mild but not significant changes in O2 and CO2 alveolar exchange efficiency and lung compliance (P-V curve) of treated animals in comparison to pair fed controls. Plasma average concentrations of amiodarone and its main metabolite, desethylamiodarone, after four weeks were 2.46 +/- 0.18 and 0.73 +/- 0.13 micrograms/ml, respectively, in the 50 mg/kg/12 hr group. In the same group amiodarone and desethylamiodarone concentrations in lung were 163 +/- 26 and 569 +/- 153 times higher than those in plasma. A highly significant correlation was found between amiodarone concentrations in plasma and lung and phospholipid content in the lung. A subgroup of animals received amiodarone 50 mg/kg/12 hr for 8 weeks. The pulmonary phospholipidosis-like lesions were similar to those observed after one month of treatment, no fibrosis was evident on light microscopic examination.

Amiodarone↗

Pattern-reversal visual evoked potentials in phenylketonuric children.

Pattern-reversal visual evoked potentials (PR-VEPs) and EEG were recorded in 14 phenylketonuric (PKU) children on a low-phenylalanine (phe) diet; the data obtained were correlated with metabolic parameters, namely, the actual phe plasma level, the mean phe plasma level in the last year, an the beginning of the diet. PR-VEPs seem to be more sensitive than EEG in detecting neurophysiological derangements in these subjects; in fact PR-VEPs were pathological in six patients while EEG detected three; no significant alterations were found in the neurophysiological tests among the children with good metabolic control, and only one child was abnormal among the six on an early dietetic regimen; in contrast, six of the nine subjects presenting with high mean phe plasma levels (greater than 10 mg/100 ml) and five of the eight whose diet started after the 2nd month of life showed pathological PR-VEPs.

Adolescent↗

Superoxide dismutase and the reduction of reperfusion-induced arrhythmias: in vivo dose-response studies in the rat.

Using anesthetized rats we have investigated the dose-response characteristics for the ability of superoxide dismutase (SOD) to reduce the vulnerability of the rat heart to reperfusion-induced arrhythmias in vivo. Hearts (n = 15 in each group) were subjected to 7 min of regional ischemia followed by 10 min of reperfusion. In the control group (saline), 73% (11/15) of the hearts fibrillated during reperfusion, 20% (3/15) had atrioventricular block and 47% (7/15) died as a result of ventricular arrhythmias. Superoxide dismutase, administered as an intravenous bolus 2 min prior to reperfusion exerted a marked protective effect. At its most effective dose (10 mg/kg body wt i.e. 27,000 IU/kg body wt) reperfusion-induced ventricular fibrillation was reduced to 33% (5/15). Reperfusion-induced atrioventricular block was eliminated (0/15) and mortality was reduced to 7% (1/15, p less than 0.05). The protective effects were however very dose-dependent and at higher doses SOD exhibited no antiarrhythmic actions during reperfusion. These results, together with our previous findings in vitro, lend further support to our proposition that oxygen-derived free radicals may play a role in the induction of potentially lethal cardiac arrhythmias and that antifree radical interventions, even when given after the onset of ischemia, can be highly protective.

Animals↗

Myopathy during amiodarone treatment: a case report.

The case of a 69-year-old woman who developed muscle weakness on chronic amiodarone treatment is reported. Muscle biopsy showed vacuolar alterations and a marked accumulation of amiodarone and of its metabolite desethylamiodarone was found in the muscle sample despite normal blood levels. Amiodarone-induced morphological alterations of the muscle may be related to the actual tissue concentration rather than to the blood level.

Aged↗

Effects of three new anthracyclines and doxorubicin on the rat isolated heart.

The acute cardiac toxicity of three second-generation anthracycline analogues and doxorubicin was compared in a model of the rat isolated Langendorff perfused heart. The drugs, doxorubicin (DX), 4-epi-doxorubicin (4'EDX), 4-demethoxy-daunorubicin (4DMDR) and 4'-deoxy-doxorubicin (4'dxDX) were infused for 40 min at a concentration of 26 microM into the isolated hearts. All four compounds significantly reduced cardiac work and its first derivative. The time to 50% decrease in work (TW50) was respectively 36, 23, 9 and 7 min for DX, 4'EDX, 4'dxDX and 4DMDR. The three anthracycline derivatives, but not DX, significantly increased coronary resistance. Heart rate was reduced by all compounds compared with baseline, but not compared with controls. Rhythm disturbances were seen with all five hearts perfused with 4DMDR, which stopped beating before 40 min; 2/5 hearts in the 4'EDX group and 1/5 hearts in the 4'dxDX group also stopped before the end of perfusion. All the compounds reached concentrations in the myocardium 8 to 50 times higher than in the perfusing medium. The more cardiotoxic the compound, the higher was its myocardial concentration; a significant correlation was found for all four agents. Noradrenaline was never measurable in the perfusate of control and DX hearts; perfusion with the three anthracycline derivatives caused some release, but the pattern was not clearcut and the maximum concentrations attained in the perfusate were relatively low (less than or equal to 1.6 X 10(-9) M). In conclusion, in the rat isolated perfused heart, the early cardiotoxicity induced by equimolar concentrations of the three anthracycline compounds was greater than that induced by DX and was directly related to drug accumulation in the myocardium. Catecholamines do not seem to have a major role in the development of toxicity in this model.

Animals↗

Amiodarone and desethylamiodarone tissue uptake in rats chronically treated with amiodarone is non-linear with the dose.

Four groups of rats were given amiodarone chronically at 25, 37.5, 50, 75 mg kg-1/12 h for 3 weeks; on day 21 the animals were killed and blood, plasma, heart, lung, liver and fat were collected and assayed for amiodarone and desethylamiodarone. Amiodarone plasma concentrations ranged from 0.74 to 4.68 micrograms mL-1 and desethylamiodarone from 0.08 to 2.05 micrograms mL-1. Plasma, blood and tissue concentrations of amiodarone and desethylamiodarone increased significantly with the dose. Blood/plasma and tissue/plasma partition ratios of amiodarone and desethylamiodarone increased significantly at the higher doses. Blood/plasma ratio was a good predictor of tissue/plasma ratios of amiodarone and its metabolite, except in fat. Total phospholipid concentrations in lung were correlated with amiodarone and desethylamiodarone concentrations in plasma, blood and lung.

Amiodarone↗

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History of Pharmacy↗