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Biomedical subjects

G Pezzoli

Publications and source records attributed to G Pezzoli.

At least 55 records · Page 3Linked to original sources

n-hexane induces parkinsonism in rodents.

A case of human parkinsonism, due to n-hexane exposure, was recently described. On the basis of this observation, we treated mice and rats with n-hexane and its principle toxic metabolite 2,5-hexanedione. The mice underwent a chronic treatment intraperitoneum, the rats were treated stereotaxically into the substantia nigra. At biochemical analysis of the striata, dopamine and homovanillic acid levels were significantly lower compared with control animals; norepinephrine, serotonin, 5-hydroxindolacetic acid levels were unchanged. The rats treated with 2,5-hexanedione showed an apomorphine-induced rotational behavior significantly higher compared to controls. Since n-hexane and its metabolites are environmental contaminants and by-products of endogenous metabolic pathways, we propose that they may play a role in inducing parkinsonism in humans.

Animals↗

Monoamine oxidase inhibitory properties of milacemide in rats.

Milacemide is a glycine prodrug with reported antiepileptic antimyoclonic properties. In this study, milacemide increased "wet dog shakes" in rats pretreated with 5-Hydroxytryptophan (5-HTP) and carbidopa. Moreover, it worsened the serotonin behavior syndrome precipitated by 5-HTP and the monoamine oxidase inhibitor tranylcypromine. The serotonin syndrome was also elicited by the combination of milacemide and 5-HTP without tranylcypromine. In vitro, milacemide inhibited both monoamine oxidase A and B from the frontal cortex of rats, to a greater extent for MAO B. This drug is currently under investigation in humans as an antiepileptic agent and precautions for the consequences of monoamine oxidase inhibition should be considered when the drug is used in high doses.

5-Hydroxytryptophan↗

Milacemide increases 5-hydroxytryptamine and dopamine levels in rat brain--possible mechanisms of milacemide antimyoclonic property in the p,p'-DDT-induced myoclonus.

Milacemide, a glycine prodrug that is able to enter the brain readily, has been shown to have an antimyoclonic property in the p,p'-DDT-induced myoclonus syndrome. Milacemide increased regional 5-HT and dopamine and decreased 5-HIAA, DOPAC and HVA levels in naive rats. In p,p'-DDT-treated rats, 5-HT levels were unchanged at the time the rats experienced spontaneous myoclonus in all brain regions except in the striatum, where it increased. 5-HIAA levels increased but did not reach significant levels except in the striatum. Dopamine, DOPAC, HVA and norepinephrine were unchanged. When rats were treated concurrently with both p,p'-DDT and milacemide, regional 5-HT levels were increased and NE levels in the brainstem and cerebellum decreased. Depletion of brain serotonin by pretreatment with PCPA or with 5,7-DHT, or blocking 5-HT receptors with different 5-HT antagonists, failed to eliminate the antimyoclonic property of milacemide. This antimyoclonic effect of milacemide may be mediated through other mechanisms besides its ability to increase brain 5-HT levels. Possible mechanisms to be considered are its antiepileptic property, and its ability to increase brain glycine levels. Milacemide may have potential for therapeutic trials in patients with myoclonus.

Acetamides↗

Intraarticular sodium hyaluronate injections in the Pond-Nuki experimental model of osteoarthritis in dogs. II. Morphological findings.

The effect of the intraarticular sodium hyaluronate (HA) injection on the osteoarthritic knee joint has been evaluated in dogs using an experimental model of osteoarthritis induced by sectioning the anterior cruciate ligament. Seven weeks after surgery, the damage, graded according to Mankin's scale, was significantly reduced in knee joints treated with HA from the second week postsurgery compared to untreated joints. When intraarticular HA therapy was initiated after the seventh week, osteoarthritis progression was still reduced compared to controls. Both morphology and morphometry showed a beneficial effect of HA on the cartilage response to the damage, as well as a clearcut inhibitory effect on the development of the fibroblastlike cell layer on the articular cartilage in untreated joints. The beneficial effects on the cartilage integrity and response to osteoarthritic damage might be related to a primary effect of HA on the cartilage surface. However, these effects do not exclude the possibility that, in addition, HA might act on the synovial membrane by limiting the synovial reaction.

Animals↗

Non-chromaffin tissue plus nerve growth factor reduces experimental parkinsonism in aged rats.

The mechanisms by which intrastriatal grafts of chromaffin tissue alleviate the signs of clinical and experimental parkinsonism remain elusive. In the present report, we have demonstrated that, in conjunction with intraventricular infusion of nerve growth factor (NGF), ventricular grafts of either non-chromaffin or adrenal medullary tissue are equally effective in reducing apomorphine-induced circling in rats whose substantia nigra have been permanently lesioned with 6-hydroxydopamine. These treatments were much more effective than implantation of adrenal medulla without NGF. In addition, the effects persisted indefinitely, though at a reduced level, after discontinuation of the NGF infusion. The results suggest that trophic factors may be crucial to the beneficial effects of intracerebral transplanted tissues.

Adrenal Medulla↗

Cryopreservation of human fetal adrenal medullary cells.

Cryopreservation of human fetal adrenomedullary cells was performed, after dissociation of the gland and purification of chromaffin aggregates, using 10% dymethyl sulfoxide as cryoprotectant. More than 90% of thawed cultured clusters appear morphologically intact, showing extensive neurite outgrowth and absence of appreciable cellular loss. Immunoreactivity for tyrosine hydroxylase and response to nerve growth factor were demonstrated. These findings indicate that human medullary cells maintain their distinctive functional characteristics after cryopreservation.

Adrenal Medulla↗

Madopar HBS in fluctuating parkinsonian patients: two-year treatment.

In an open-label study, we substituted conventional levodopa plus benserazide: 100/25 (Madopar) with a controlled-release form (HBS) in 18 fluctuating parkinsonian patients for 24 months. Significantly positive results were obtained in both peak-dose and diphasic dyskinesias up to 12 months of treatment; morning akinesias were also improved up to 6 months. A general trend of deterioration, compared to the first 3-6 months of HBS treatment, was observed in "off" fluctuations after 1 year: akinesias due to a delayed response worsened after 1 year of treatment also when compared with the conventional treatment. Positive results were obtained with new HBS on standard Madopar-related psychiatric disorders.

Adult↗

Glycine involvement in DDT-induced myoclonus.

The DDT syndrome in rats consists of tremor, myoclonus, running seizures, hyperthermia, episodic boxing, and excessive grooming. DDT did not change whole-brain glycine levels when the rats had stimulus-sensitive myoclonus, spontaneous myoclonus, or seizures. However, regional analysis showed a decrease in glycine levels in the pons and medulla initially, but they rose again despite worsening of the myoclonus. Glycine given intraventricularly and the glycine prodrug, milacemide, given intraperitoneally suppressed DDT-induced myoclonus. A dose of milacemide that prevented DDT-induced myoclonus caused a significant increase in glycine levels in cortex, septum accumbens, cerebellum, striatum, hippocampus diencephalon, midbrain, pons, and medulla. The increase was most marked in the forebrain structures. There was no change in serine levels in these areas. These data suggest that the glycinergic system may be playing an important role in the manifestation of DDT-induced myoclonus.

Acetamides↗

Primary cultures of human caudate nucleus.

It is possible to grow functional primary dissociated cultures and explants from stereotactic biopsies of human parkinsonian caudate nuclei. Two major classes of cells were identified on morphological grounds. The culture cells appear to be stimulated by an unidentified soluble factor(s) obtained from human fetal neuronal cells in vitro. Culture of primary neuronal and glial cells from human adult cerebral nuclei seems to be a useful tool for several research purposes and in particular for studying both trophic factor action and target effects on afferent neurons for prospective human brain grafting.

Adult↗

Low doses of ketazolam in anxiety: a double-blind, placebo-controlled study.

A multicenter, double-blind, between-patient trial comparing two doses of ketazolam (15 and 30 mg) with placebo, each given once daily, in the evening, to 92 outpatients affected by generalized anxiety disorders for at least 1 month, was carried out. After 1-week washout period 47 patients were randomized to ketazolam 15 mg, and 45 to placebo for 15 days (first period). At the end of this period, if the patient experienced a decrease on the total Hamilton Anxiety Rating Scale (HAM-A) of at least 25% of basal value, the treatment was kept unchanged for a further 15 days, otherwise 15 mg of ketazolam were added to the previous treatment (second period). Anxiety was rated after 2 and 4 weeks with the Italian HAM-A scale and with a 4-point scale (patient's assessment). Seventy-eight patients completed the first period and 75 the whole study. During the first period the percentage of responders was almost identical in both treatment groups, but during the second period a further slight improvement was observed in the early placebo responders, while the HAM-A score of patients on ketazolam continued to improve significantly (p less than 0.01) throughout the study. Likewise a significant (p less than 0.001) difference between treatments was observed, on the 4-point scale, in the population as a whole (end of first period) as well as in responder patients (end second period). Tolerability was good, except in 1 patient on placebo, who was withdrawn from the study because of severe headache.

Adolescent↗