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Biomedical subjects

M Morelli

Publications and source records attributed to M Morelli.

At least 109 records · Page 6Linked to original sources

Nigral dopamine autoreceptors are exclusively of the D2 type: quantitative autoradiography of [125I]iodosulpride and [125I]SCH 23982 in adjacent brain sections.

The effect of unilateral 6-hydroxydopamine lesions of the medial forebrain bundle on the specific binding of [125I]iodosulpride and [125I]SCH 23982 in the rat substantia nigra was determined by quantitative autoradiography of adjacent sections. The specific binding of [125I]iodosulpride was reduced by 40-70% on the lesioned side in the substantia nigra pars compacta, reticulata, lateralis and in the ventral tegmental area. In contrast, the specific [125I]SCH 23982 binding was unchanged in all subdivisions of the substantia nigra. The results indicate that dopamine autoreceptors are present in the substantia nigra and in the ventral tegmental area and that they are exclusively of the D2 type.

Animals↗

Plasma melatonin levels in psoriasis.

Melatonin is synthesized and secreted by the pineal gland. A daily rhythm of melatonin secretion, with high plasma values during the dark period, has been found in all vertebrates studied so far. In psoriatics, several hormones, including GH and prolactin, have altered chronobiology, and some studies in humans suggest that melatonin affects the levels of GH and prolactin. We investigated circadian melatonin rhythm in 13 male psoriatics and 13 healthy males with an RIA specific for measuring the hormone in plasma. Samples were taken at 6 a.m., 8 a.m., 12.00, 4 p.m., 8 p.m. and 2 a.m. Differences in (mean +/- SD) plasma melatonin levels were analysed by Student's t-test. Our results show that psoriatic patients had lost the nocturnal peak and usual circadian rhythm of melatonin secretion. Levels of melatonin were significantly lower than in controls at 2 a.m., and higher at 6 and 8 a.m. and at 12 noon. Further investigations of this disorder of melatonin secretion in psoriasis are needed to understand its significance.

Adult↗

Applicability of local hyperthermia as adjuvant to systemic chemotherapy.

With the aim of verifying the in vivo applicability of local hyperthermia combined with chemotherapy, 13 patients with superficial metastases from different histologic types of carcinoma, mostly from head and neck cancer, were entered in a pilot study. The chemotherapeutic regimen was cis-platinum, 20 mg/m2/d X 5 days, bleomycin, 10 mg/m2 on days 8 and 12, methotrexate, 100 mg/m2 on day 15, followed after 24 by folinic acid. Hyperthermia, using a microwave apparatus, and chemotherapy were delivered simultaneously. Objective remissions were achieved in 54% of patients, within the hyperthermia field (1 CR and 6 PR). No serious toxicity was noted. Methotrexate distribution after local hyperthermia was evaluated in 8 patients. Response duration was not gratifying, except for patients successively treated with radiation. In conclusion, the combination of chemotherapy plus local hyperthermia deserves subsequent evaluation as part of adjunctive programs.

Aged↗

Agonist-induced homologous and heterologous sensitization to D-1- and D-2-dependent contraversive turning.

A low dose of the D-1 receptor agonist SKF 38393 (2.0 mg/kg s.c.) 14 days post-lesion failed to induce contraversive turning in male Sprague-Dawley rats lesioned unilaterally in the medial forebrain bundle with 6-hydroxydopamine (6OHDA). Priming with a single administration of the specific D-2 agonist LY 171555 (0.2 mg/kg s.c. 3 days before), which itself elicited contraversive turning, made SKF 38393 (2.0 mg/kg s.c.) very active to produce contraversive turning. Priming with LY 171555 (0.2 mg/kg s.c. 3 days before) potentiated the contraversive turning in response to a low dose of LY 171555 (0.05 mg/kg s.c.). In naive 6OHDA-lesioned rats a rather high dose of SKF 38393 (10 mg/kg s.c.) was needed to induce a low intensity contraversive turning. Priming with a single administration of SKF 38393 (10 mg/kg s.c. 3 days before) made an otherwise ineffective dose of SKF 38393 (2.0 mg/kg s.c.) very effective to produce contraversive turning. The results indicate that the sensitization to the behavioural expression of supersensitivity for a given DA-receptor type follows not only priming with agonists for the same DA-receptor type (homologous sensitization) but also priming with agonists for a different DA-receptor type (heterologous sensitization).

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

6-Hydroxydopamine lesions reduce specific [3H]sulpiride binding in the rat substantia nigra: direct evidence for the existence of nigral D-2 autoreceptors.

[3H]Sulpiride bound to substantia nigra homogenates in a saturable manner and with a pharmacological profile typical of a specific D-2 ligand. Unilateral 6-OH-dopamine (DA) lesions of the nigrostriatal DA neurons reduced by 27-46% the Bmax of the specific [3H]sulpiride binding in substantia nigra homogenates depending on the time after 6-OHDA lesion and significantly increased the Bmax in the caudate. KDs remained unchanged in both areas. The localization of specific [3H]sulpiride binding and its reduction in the substantia nigra of the 6-OHDA-lesioned side were confirmed by quantitative autoradiography. The results provide evidence for the existence of D-2 autoreceptors in substantia nigra.

Animals↗

Behavioural expression of D-1 receptor supersensitivity depends on previous stimulation of D-2 receptors.

SKF 38393 (2 mg/kg s.c.), a reportedly selective D-1 agonist, failed to induce contralateral turning behaviour in naive rats bearing 12 days old unilateral 6-hydroxydopamine lesions. On the other hand strong contraversive turning in response to SKF 38393 was obtained if rats had been tested 2 or 7 days before with apomorphine (0.1 mg/kg s.c.) or with LY 171555 (0.2 mg/kg s.c.), a selective D-2 receptor agonist. Contraversive turning in response to SKF 38393 was blocked by a low dose (0.05 mg/kg s.c.) of the specific D-1 antagonist SCH 23390. The results indicate that the behavioural expression of D-1 receptor supersensitivity following lesion of dopaminergic neurons depends on previous exposure to a stimulation of D-2 receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Antagonism of apomorphine-induced yawning by SCH 23390: evidence against the autoreceptor hypothesis.

The ability of apomorphine to induce yawning (YWG) in normal and reserpinized rats and its interaction with SCH 23390, a potent and specific D-1 receptor antagonist, was studied. Apomorphine was more potent in inducing YWG in reserpine-pretreated as compared to control rats. SCH 23390, in low doses (0.05 mg/kg SC), was able to significantly reduce the YWG evoked by apomorphine both in control and in reserpine-pretreated rats. The results indicate that D-1 receptors contribute to YWG elicited by apomorphine and contradict the idea that this effect is mediated by DA autoreceptors.

Animals↗