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Biomedical subjects

D Rotiroti

Publications and source records attributed to D Rotiroti.

At least 37 records · Page 2Linked to original sources
PubMed1995

NMDA-dependent prostaglandin E2 release by human cultured astroglial cells is driven by nitric oxide.

The role of the L-arginine-NO pathway on the formation of PGE2 by human cultured astroglial cells incubated with NMDA has been investigated. Preincubation of T 67 astroglial cell line with NMDA (10-600 microM) produced a significant dose-dependent increase of both nitrite (the breakdown product of NO), PGE2 and cGMP levels in cell supernatant. This effect was inhibited by coincubation of cells with L-NAME (20-300 microM), an inhibitor of NO synthase showing that the release of PGE2 subsequent to NMDA receptor stimulation was driven by NO. The release of PGE2 but not elevation of nitrite and cGMP levels was affected by indomethacin (10 microM), an inhibitor of cyclooxygenase. The inhibitory effect of L-NAME on PGE2 release by NMDA-pretreated astroglial cells was reverted by arachidonic acid, showing that the effect of NO on PGE2 release occurred at the cyclo-oxygenase level. Thus, the present experiments demonstrate that the release of PGE2 by astroglial cells pretreated with NMDA is driven by activation of the L-arginine-NO pathway, and this may be relevant in the pathophysiological mechanisms where glutamatergic neurotransmission is involved.

Arachidonic Acid↗
PubMed1995

Age-dependent changes of NO synthase activity in the rat brain.

We report that NO synthase activity, as expressed by citrulline and nitrite formation in brain homogenates, is decreased in 24-month old in comparison to 3-month old rats. In particular, a Ca(++)-dependent NO synthase activity was detected in homogenates obtained from cortical, hippocampal, cerebellar and lower brain stem slices from both 3- and 24 month-old rats. The amount of citrulline generated from L-arginine was significantly decreased in the hippocampus and lower brain stem by 40 and 48%, respectively. No changes were observed in NO synthase activity in cortical and cerebellar homogenates. Thus, the L-arginine-NO pathway seems to be impaired in selected areas of rat brain and this may contribute to the understanding of pathophysiological mechanisms underlying age-related cerebral disorders.

Aging↗
PubMed1994

[The prevention of nitrate tolerance in angina patients treated with transdermal nitroglycerin: a comparison of 2 therapeutic regimens (therapeutic outlook versus dosage reduction)].

We studied the long-term antianginal and anti-ischemic effects of two dosage regimens designed to prevent tolerance to transdermal nitroglycerin (TNTG): (1) 10 mg TNTG applied for 16 h with a 'nitrate-free' interval of 8 h; (2) 10 mg TNTG applied for 16 h followed by a 'nitrate-low' interval of 5 mg applied for 8 h. 129 patients completing a 3-month study period were evaluated by repeated exercise tests. Both regimens significantly increased maximum exercise duration at 3 months, from 699.1 +/- 23.4 to 833 +/- 21.9 s and from 686.1 +/- 20 to 789.6 +/- 22.6 s, respectively, reduced the number of patients with 1 mm S-T segment depression and increased the time duration to 1 mm S-T segment depression. Marked reductions in anginal attacks was observed in both groups: from 6.5 to 0.15 attacks per week and from 6.0 to 0.15 attacks per week, respectively. No statistically significant differences were found between the groups, and both regimens were well tolerated. In conclusion, our results demonstrate sustained antianginal efficacy, without tolerance, of either 'nitrate-free' of 'nitrate-low' interval therapy with transdermal nitroglycerin.

Administration, Cutaneous↗
PubMed1994

Neurodegeneration produced by intrahippocampal injection of paraquat is reduced by systemic administration of the 21-aminosteroid U74389F in rats.

The behavioural, electrocortical (ECoG) and neurodegenerative effects of intrahippocampal injection of paraquat, a well-known free radical producing agent, were studied in rats. Injection of paraquat (100 nmol) into one dorsal hippocampus produced limbic motor and ECoG seizures. These effects were accompanied at 24 h by severe damage to CA1, CA3 and CA4 hippocampal pyramidal neurones and dentate gyrus granule cells. In comparison to the cell number counted in control, untreated, side of the hippocampus, significant (P < 0.05) neuronal loss was observed in the CA1 and CA3 pyramidal cell layers of the treated hippocampus. A lower dose of the herbicide (10 nmol) did not produce consistent motor and ECoG effects and in no instance was significant neuronal loss observed. A pretreatment with U74389F [21-4-(2,6-di-l-pyrrodinyl-4-pyridinyl)-1-piperazinyl-pregna-1,4,9 (11)triene-3,20-dione monomethansulfonate] (30 mg/kg i.p., 15 min before paraquat) completely protected rats from motor and ECoG epileptogenic effects induced by intrahippocampal paraquat (100 nmol). This dose of U74389F also reduced the hippocampal damage typically produced by paraquat and no significant neuronal loss was reported in the CA1 and CA3 pyramidal cell layers. A lower dose of U74389F (10 mg/kg i.p.) did not afford any protection against the epileptogenic effects produced by paraquat (100 nmol); in these animals hippocampal damage was still evident though neuronal loss did not reach statistical significance. In conclusion, the present data show that systemic administration of U74389F possesses neuroprotective effects against seizures and neurodegeneration typically elicited by intrahippocampal injection of paraquat.

Animals↗
PubMed1992

Epileptogenic effects of skin extracts from the Australian frog Pseudophryne coriacea after intracerebral microinfusion in rats.

The behavioural and electrocortical (ECoG) effects induced by a methanol extract of the skin of the Australian frog Pseudophryne coriacea, directly microinjected into several areas of the brain, were studied in freely moving rats. Administration of the P. coriacea extract (5, 10, 15 and 20 micrograms) into the dorsal hippocampus produced a dose-dependent and reversible behavioural stimulation and ECoG spikes lasting 20-140 min. Similar but less intense effects were elicited in rats receiving injections into the III cerebral ventricle, amygdala and caudate nucleus. In conclusion, the present experiments show that the skin extract of P. coriacea produces behavioural stimulation and ECoG spikes when injected into the rat brain, the most sensitive area being the hippocampus.

Amphibian Venoms↗
PubMed1991

A case of portal thrombosis arisen after treatment with dihydroergotamine.

We describe the case of a 42 year old woman with abdominal pain, ascites, and splenomegaly after having taken dihydroergotamine continuously for three months due to frequent hemicranic episodes. The celiac-mesenteric angiography demonstrated diffuse thrombosis of splenic, superior mesenteric and portal veins. No surgical intervention was possible. We believe that it is possible that dihydroerogotamine, a hydrogenated derivative of ergotamine, inasmuch as it is capable of causing peripheral vasoconstriction, intimal lesions, arterial and venous thrombi, was also the cause of our patient's portal thrombosis. We therefore suggest the minimum effective amount of the drug be utilized to achieve the relief of cephalalgia.

Adult↗
PubMed1991

Ultrastructural changes of crop-sac and lactotrophs after systemic or intraventricular administration of drugs enhancing cholinergic transmission in pigeons.

The ultrastructural effects of drugs enhancing, by different mechanisms, cholinergic transmission in the crop-sac (the target for prolactin secretion in birds) and the anterior pituitary lactotrophs, were studied in pigeons (Columba livia). The systemic or intraventricular administration of physostigmine, carbachol and muscarine produced maximal crop-sac stimulation with milk-like secretion, as demonstrated by the observation of ultrastructural changes in the lactiferous areas through scanning and transmission electron microscopy of the crop-sac mucosa. A marked activation was also observed in anterior pituitary lactotrophs. Crop-sac and anterior pituitary lactotrophs stimulatory effects were prevented by an atropine pretreatment, but not by mecamylamine and pempidine pretreatments. The present results suggest that muscarinic receptors at the hypothalamic and/or anterior pituitary level are involved in avian species in the control of prolactin secretion.

Animals↗
PubMed1988

Anticonvulsant effects of avermectin in DBA/2 mice and rat.

The anticonvulsant activity of avermectin B (AVM) was studied after systemic administration in DBA/2 mice (seizures induced by sound) and rats (seizures induced by pentylenetetrazol, cephazolin and maximal electroshock test). Protection against sound-induced seizures was given after intraperitoneal administration of AVM (30 and 50 mg/kg). Cephazolin-induced seizures in rats were attenuated by intraperitoneal administration of AVM (10 and 20 mg/kg). AVM increased the antipentylenetetrazol activity of diazepam. No significant protection against the tonic component in the electroshock test was observed. Behavioural effects of AVM included signs of sedation in both mice and rats. In all, these results indicate that, besides its specific anthelmintic effects, AVM possesses anticonvulsant properties, the mechanism(s) of which still remain to be elucidated.

Animals↗
PubMed1987

Evaluation of cefotaxime concentrations in rat cerebral areas and serum by microbiological method and HPLC.

The aim of the investigation was to verify the reliability and sensitivity of High Performance Liquid Chromatography (HPLC), compared to the classic microbiological method of plate diffusion, in evaluating cefotaxime concentrations in some cerebral areas and serum of the rat. The mean concentration of cefotaxime in the serum (after acute administration of 15 mg/kg i.m.) was 20 micrograms/ml with the microbiological method and 23 micrograms/ml with HPLC. No antibiotic was detectable, with both methods, in the cerebral areas. The results with both methods are in good accordance, although the HPLC technique is more sensitive and accurate.

Animals↗
PubMed1984

Long-lasting hypothermic effects of vincristine in rats.

The effects of vincristine given intravenously on deep and superficial body temperature were assessed in rats kept at ambient temperature within the thermoneutral range. Vincristine (0.5 and 1 mg/kg i.v.) produced a gradual but marked hypothermic response which was dose-dependent, reached its maximum after approximately 3 h and lasting approximately 48 h. Vincristine induced a decrease in deep body temperature which was accompanied by piloerection and a decrease in skin temperature. Pretreatment with phentolamine, an alpha-adrenoceptor blocking agent (0.5 mg/kg i.v. 15 min before) prevented the hypothermic effects induced by subsequent administration of vincristine (0.5 mg/kg i.v.). These experiments showed that vincristine produced a marked hypothermic response in rats. However, the precise site of action remains to be established.

Animals↗
PubMed1984

Stimulation of crop sac and pituitary lactotrophs after intraventricular administration of dermorphin in pigeons.

The effects of dermorphin, a new potent opioid peptide, on structural and ultrastructural changes in the crop sac and in pituitary lactotrophs were assessed in pigeons (Columba livia). A single administration of dermorphin into the third cerebral ventricle (1 microgram) and the same dose repeated for 3 consecutive days both produced maximal crop sac stimulation, as documented by the presence of milk-like material as well as by scanning and transmission electron microscopy of crop sac mucosa. In addition, marked stimulatory effects were also observed in pituitary lactotrophs, as shown by stimulation of Golgi apparatus, enlargement of rough endoplasmic reticulum, increase in mitochondria size, and the presence of lysosomes and electron-opaque granules. The stimulatory effects of dermorphin on the crop sac and lactotrophs were completely prevented by naloxone, an antagonist at opiate receptors. Since dermorphin is a natural constituent of the avian brain, it has been suggested that this peptide may represent the still-obscure hypothalamic prolactin stimulatory factor.

Animals↗
PubMed1984

Effects of tetanus toxin after intracerebral microinjection are antagonized by drugs enhancing GABAergic transmission in adult fowls.

In adult fowls (Gallus domesticus), the behavioural effects of small doses of tetanus toxin, after unilateral microinjection into the nucleus mesencephalicus profundus (NMP), homologous to the mammalian substantia nigra, were studied. A rich pattern of stereotyped movements, vocalization, ipsilateral head-neck rotation, wing abduction, occasional ipsilateral circling and escape responses from the box were observed; the intensity of such symptomatology was dose-related and fully reversible within approx. 4 hr. Pretreatment with sodium valproate (100 and 200 mg/kg, i.m.) or with ethanolamine-sulphate (EOS, 1.6 mumol into the NMP) completely prevented the effects of tetanus toxin. The present findings show that fowls can represent an ideal species for studying acute central effects of tetanus toxin and more interestingly that drugs enhancing GABAergic mechanisms are able to prevent the effects of tetanus toxin.

Animals↗