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A Zanotti

Publications and source records attributed to A Zanotti.

36 records · Page 2Linked to original sources

Chronic phosphatidylserine treatment improves spatial memory and passive avoidance in aged rats.

Learning/memory deficits in senescent animals are widely used as a tool to evaluate the therapeutic potential of agents for treatment of age-associated cognitive dysfunction. As assessed in the Morris water maze test, aged (21-24 months) rats showed a variable loss of spatial memory. Aged non-impaired rats performed as well as young subjects, while aged impaired rats exhibited a severe and persistent place-navigation deficit. Passive avoidance retention was similarly affected in the two aged subpopulations. Chronic oral administration of phosphatidylserine (50 mg/kg/day for up to 12 weeks), a pharmacologically active phospholipid, was found to improve both the spatial memory and the passive avoidance retention of aged impaired rats. Results are discussed with reference to the phosphatidylserine-induced improvement of age-associated deterioration of brain functions in rats.

Aging↗

Dihydroergocristine in stopping lactation: double-blind study vs bromocriptine.

In a double-blind study vs bromocriptine, 30 women who wished to interrupt breast-feeding after a physiological delivery and at least 3 months of nursing were given at random 10 mg dihydroergocristine capsules or 2.5 mg bromocriptine capsules twice a day for 5 days, then 3 times a day for 5 days if treatment had failed to produce an effect. The parameters considered were PRL plasma levels, which were measured at baseline, on the 5th day and, where necessary, on the 10th day of treatment. Milk secretion, breast swelling and pain were recorded at baseline and daily during treatment. The appearance of any side-effect was accurately reported. A prolactin decrease was observed in both groups (p less than 0.01). After 5 days milk secretion was reduced more significantly in the dihydroergocristine group; after 10 days of treatment 6 cases treated with bromocriptine and 1 case treated with dihydroergocristine still revealed a low milk secretion. Breast congestion and pain were absent in both groups. As regards side-effects, a significant decrease in systolic blood pressure (standing position) was reported in the bromocriptine group. Other symptoms, such as nausea, vomiting, insomnia and headache, were reported in 8 patients in the bromocriptine group vs 6 patients in the dihydroergocristine group.

Adult↗

Dihydroergocriptine in management of microprolactinomas.

The effects of dihydroergocriptine (DHECP), a dihydrogenated ergot alkaloid with dopaminergic agonistic and alpha-adrenergic antagonistic properties, were studied in 22 women with PRL-secreting microprolactinomas and compared with those recorded in 36 previously studied patients treated with bromocriptine (BRC). After acute administration of 5 mg DHECP, orally, serum PRL decreased by 61 +/- 18% (+/- SD); only 1 patient was unresponsive. The nadir was reached at 300 min. Long term treatment with increasing DHECP doses caused a progressive PRL fall from 125 +/- 142 (+/- SD) to 81 +/- 159 micrograms/L after 1 week of a 3 mg twice daily regimen, to 64 +/- 88 micrograms/L after 1 week of 5 mg twice daily, 46 +/- 57 micrograms/L after 1 week of 10 mg twice daily, and 28 +/- 34 to 33 +/- 45 micrograms/L throughout 9 months of treatment with 10 mg DHECP 3 times daily. Seventy-seven percent of patients had normal serum PRL levels during chronic treatment. All women, including those with supranormal serum PRL levels, resumed regular menses, and 16 had ovulatory cycles; 1 woman became pregnant. Galactorrhea disappeared in all. During treatment the PRL response to TRH, initially absent in all patients, became positive in 10. In 7 patients, after DHECP treatment for 9 months, high definition computed tomographic scan no longer showed the focal lesions initially seen. After drug withdrawal, serum PRL increased again in all except 1 patient. Two patients had regular menses for 6 months, and 3 still had no adenoma imaged by high definition computed tomography. In BRC-treated patients the serum PRL changes and clinical results were very similar to those in the DHECP-treated patients, except for the persistence of normal serum PRL levels in 4 patients after drug withdrawal. On the other hand, side-effects were negligible during DHECP treatment, but remarkable during BRC. Systolic and diastolic blood pressures decreased by only 5.4 and 3.0 mm Hg, respectively, after acute 5 mg DHECP administration, but decreased by 12.8 and 14 mm Hg after acute 2.5 mg BRC administration. Orthostatic hypotension and peripheral vasomotor phenomena occurred in the long term DHECP treated patients except one, but they occurred in 9 and 3 of those treated with BRC, respectively. Gastric discomfort or mild nausea occurred in 12 DHECP-treated patients, while mild or severe nausea or vomiting were observed in 18, 11, and 2 of those taking BRC, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Activity of phosphatidylserine on memory retrieval and on exploration in mice.

Recent human and animal studies have reported about neurochemical and behavioral changes occurring during aging. Bovine brain phosphatidylserine (BC-PS) administered in vivo was reported to produce changes in the metabolic status of the brain and in behavioral performances. Within the Albino-Swiss strain of mice two subtypes have been shown to exist with different learning and memory retention abilities. These animals also have different reactions to various psychoactive drugs. The experiments presented here deal with the hypothesis that BC-PS may show different effects according to the starting emotional status of the animals. The technique of intracerebral injection was employed to ensure active concentrations of BC-PS in the brain. The results reported here show that BC-PS clearly improves performances in the subtype of mice with poor exploratory activity.

Administration, Oral↗

Reversal of scopolamine-induced amnesia by phosphatidylserine in rats.

Scopolamine (2 mg/kg IP) and propranolol (55 mg/kg IP), given before a single learning trial, reduce retention of a passive avoidance response in rats. Phosphatidylserine, 30-60 mg/kg IP, antagonizes the amnesic effect of scopolamine but not that of propranolol. The retention of the passive avoidance response is not affected by phosphatidylserine given alone. The results indicate that this phospholipid selectively counteracts the action of scopolamine on passive avoidance acquisition, probably via a cholinergic mechanism.

Amnesia↗

Hypoxia-induced endotoxemia in primates: role of reticuloendothelial system function and anti-lipopolysaccharide plasma.

Acute hypoxia is known to cause a marked reduction in intestinal and peripheral blood flow, in favor of blood flow to the brain and heart. Complete occlusion of the intestinal circulation is known to damage the gut wall, allowing potentially lethal endotoxins present within the intestines to escape into the circulation. We examined here whether the breathing of a hypoxic gas mixture could lead to sufficient damage of the intestinal wall to cause endotoxemia. Six anesthetized monkeys breathed air for 1 hr, then an hypoxic mixture (FIO2 = 0.13) containing N2O for 1 h and, finally, 100% O2. Plasma endotoxin concentrations were determined by two methods. After approximately 40 min of hypoxia, the plasma endotoxin level rose significantly from 0.39 to 1.60 ng X ml-1 (p less than 0.001) and then subsided to near control levels. Control monkeys breathing air only or 70% N2O in oxygen (FIO2 = 0.3) for 3 h showed no such elevation in plasma endotoxin concentration. We conclude that hypoxia leads to a temporary endotoxemia in primates. Reticuloendothelial system depression by whole body X-irradiation (200 rads) increased both the magnitude and duration of the hypoxia-induced endotoxemia. Prior administration of equine anti-lipopolysaccharide (anti-LPS) hyperimmune plasma greatly reduced the magnitude of the induced endotoxemia. Since endotoxemia may be lethal, the use of anti-LPS as possible prophylaxis should be considered in persons breathing artificial atmospheres or where acute hypoxia may be a danger.

Animals↗

Experimental models of aging and quinolinic acid.

The normal aging process results in many functional deficits in which the central nervous system (CNS) plays a primary role. However, the study of brain aging involves numerous difficulties, including not only the complex anatomical and functional organization of the brain itself, but also because the length of the experiments themselves and experimental costs are often crucial limitations. This highlights an ever increasing need for the development of alternative model systems capable of mimicking at least to some degree the main alterations observed during the normal aging process. A comparative study of electrophysiological and behavioural features in aged rats and in young rats following chronic administration of a naturally occurring brain metabolite, quinolinic acid (QUIN), recently demonstrated to increase in the cerebral cortex of rats as a function of age, is reported. In rats there occurs an age-dependent increase in the number of animals displaying spontaneous asymptomatic spike-wave discharges, associated with impaired performance in the passive avoidance test. Chronic oral administration of QUIN to young rats also results in cortical spiking activity, without any detectable neuronal cell damage at cortical or hippocampal levels, associated with behavioural deficits similar to those observed in old rats. The utilization of young, QUIN-treated animals may thus perhaps offer an alternative model system for the comprehension of the mechanisms involved in some age-related functional impairments.

Aging↗

Serine phospholipids and aging brain.

For many years phospholipids have been studied mainly for their possible use as membrane models or cell-like carriers. Recently, on the basis of the new knowledge on the phospholipid membrane structure and function, a novel interest has arisen on the pharmacological properties of these compounds particularly at cerebral level. In this context particular attention has been devoted to phosphatidylserine (BC-PS), an anionic phospholipid extracted and purified from bovine brain, which in young animals has been shown to modify a number of brain electrophysiological and biochemical parameters.

Aging↗

Synergistic effect of phosphatidylserine with gamma-aminobutyric acid in antagonizing the isoniazid-induced convulsions in mice.

The influence of phosphatidylserine (PS) on the isoniazid-induced convulsions has been studied in mice. Sonicated dispersions of this phospholipid given intravenously do not show anticonvulsant activity but they do so when gamma-aminobutyric acid (GABA) is simultaneously injected. GABA alone is inactive. The synergism between PS and GABA is influenced by the structure of the phospholipid liposomes. In contrast to multilamellar vesicles, oligolamellar vesicles are active. Under these conditions the effect shows head group specificity, in that the neutral phosphatidylcholine (PC) or the acidic phosphatidylinositol (PI) are inactive, either in the presence or in the absence of GABA. Lysophosphatidylserine (lysoPS), the deacylated PS derivative, shows increased efficacy as an isoniazid antagonist in the presence of GABA, and has anticonvulsant activity also in the absence of GABA. Other lysophospholipids are inactive. It is suggested that PS, after its metabolic conversion to lysoPS, enhances the anticonvulsant effect of GABA.

Animals↗

Effects of phosphatidylserine on avoidance relearning in rats (preliminary observations).

During six learning sessions in a shuttle-box avoidance situation, male Sprague-Dawley rats show two kinds of learning efficiency which allow for dividing them in the subgroups of high-responding (HR) and low-responding (LR) animals. The effect of phosphatidylserine, a pharmacologically active phospholipid obtained from bovine brain, has been studied on the relearning phase of these two populations of rats. Chronic administration of phosphatidylserine (15 mg/kg i.p. for 30 days) significantly increased the avoidance performances of LR animals, without changing those of HR rats. The results obtained suggest that the different behavioral response to the phosphatidylserine treatment may depend on the pre-drug baseline of avoidance learning capability and on the effect that the drug exerts on some brain neurotransmitter metabolism.

Animals↗

Interaction of cytochrome c with cytochrome c oxidase. Photoaffinity labeling of beef heart cytochrome c oxidase with arylazido-cytochrome c.

Cytochrome c derivatives labeled with a 3-nitrophenylazido group at lysine 13, at lysine 22, or at both residues have been prepared. The interaction of the cytochrome c derivatives with beef heart cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1) in the presence of ultrviolet light results in formation of a covalent complex between cytochrome c and the oxidase. Using the lysine 22 derivative, the polypeptide composition of the oxidase is not modified, nor is its catalytic activity, whereas with the lysine 13 derivative, the gel electrophoretic pattern is altered and the catalytic activity of the complex diminished. The data are consisten with a specfic covalent interaction of the lysine 13 derivative of cytochrome c with the polypeptide of molecular weight 23,700 (Subunit II) of cytochrome c oxidase.

Affinity Labels↗

Age-dependent spontaneous EEG bursts in rats: effects of brain phosphatidylserine.

During aging, male Sprague-Dawley rats display increasing frequency of bursts of seizure-like EEG patterns. They also have a decreased retention of passive avoidance response and a loss of spontaneous alternation in a Y maze. A study was made on the effects of chronic administration of phosphatidylserine in aged rats. It was found that BC-PS reduced by 65% the number of seizures, and by 70% their duration. It also facilitated retention of passive avoidance and of spontaneous alteration behavior. These results suggest that phosphatidylserine can affect electrophysiological and behavioral parameters in aged rats probably by counteracting age-related biochemical changes.

Aging↗