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Biomedical subjects

C Ferretti

Publications and source records attributed to C Ferretti.

72 records · Page 4Linked to original sources

Calmodulin antagonism and growth-inhibiting activity of triphenylethylene antiestrogens in MCF-7 human breast cancer cells.

The triphenylethylene antiestrogen tamoxifen has been shown previously to inhibit both calmodulin and protein kinase C activities, which are involved in the control of cell proliferation. We have studied the effect of several derivatives of the triphenylethylene antiestrogen family on the inhibition of both calmodulin-dependent cyclic adenosine 3':5'-monophosphate-phosphodiesterase activity and proliferation of breast cancer cells cultured with 0.5 microM estradiol in order to prevent interaction of these drugs with the estrogen receptor. We have observed that hydroxylation of the triphenylethylene molecule significantly decreases its ability to inhibit the calmodulin-dependent phosphodiesterase activity in vitro. Furthermore, the growth-inhibiting activity of several antiestrogens and other calmodulin antagonists [R24571, trifluoperazine, N-(6-aminohexyl)-5-chloronaphthalene-1-sulfonamide, and N-(6-aminohexyl)-1-naphthalenesulfonamide] correlated with their antagonistic effects on calmodulin activity. The level of activity was determined as follows: R24571 greater than tamoxifen = N-demethyltamoxifen = nafoxidine greater than 4-hydroxytamoxifen greater than 3,4-dihydroxytamoxifen = trifluoperazine greater than N-(6-aminohexyl)-5-chloronaphthalene-1-sulfononamide greater than metabolite A greater than N-(6-aminohexyl)-1-naphthalenesulfonamide. On the other hand both protein kinase C-activating and -inhibiting drugs (phorboltetradecanoate-13-acetate and tamoxifen, respectively) have a synergistic inhibitory effect on the growth of MCF-7 cells. Our data suggest that antiestrogen interactions with calmodulin and not protein kinase C may play a role in mediating the drug-induced estrogen-independent inhibition of breast cancer cell growth.

3',5'-Cyclic-AMP Phosphodiesterases↗

[Effect of street noise on blood catecholamines, cyclic AMP and various cardiovascular and metabolic functions in a group of subjects with untreated essential hypertension].

The effect of road noise on blood catecholamines, cAMP and certain cardiovascular and metabolic parameters was studied in a group of young untreated essential hypertensives. It was found that the 10' stimulus increased both systolic and diastolic pressure values. Blood catecholamines rose only after 5'. The most significant increase was in adrenaline as opposed to noradrenaline and dopamine. Significant changes were noted in cAMP and triacylglycerols (10' and 15' after commencement of the stimulus respectively). Comparison with previous results in normotensives suggested that the catecholamine response to stress is primarily alpha-receptorial when blood pressure is normal and beta-adrenergic in hypertension.

Adult↗

Further studies on the effects of heroin addiction on the hypothalamic-pituitary-gonadal function in man.

The effects of chronic heroin addiction on LH biological and immunological activity, as well as on total and free testosterone concentrations, were investigated in 8 active young male addicts. The results were compared with those obtained in 33 normal young men. In addition, the effects of naloxone (N) administration on LH bio- and immuno-potency were studied in 3 normal men. LH biological activity (bLH) was assessed by a specific and sensitive "in vitro" bioassay, based upon testosterone production by mechanically dispersed mouse Leydig cell preparations. Double antibody radioimmunoassay methods were employed to assess serum levels of immunoreactive LH (iLH), total testosterone (T) and morphine (M). Free testosterone (FT) concentrations were determined by RIA after an ultrafiltration procedure. Mean basal values of bLH, iLH, T and LH bio/immuno (b/i) ratio observed in heroin addicts were similar to those obtained in the control group. In contrast, serum levels of FT and the mean FT/T ratio were significantly reduced in heroin addicts. A significant decrease of LH b/i ratio was observed during N infusion in the normal subjects.

Adolescent↗

Biochemical effects of minaprine on striatal dopaminergic neurons in rats.

The biochemical effects of minaprine, a new psychotropic drug, were investigated on striatal dopaminergic neurons in the rat. Minaprine did not displace [3H]spiperone in-vitro binding from striatal membranes but had clear effects on dopamine (DA) metabolites. Homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC) were significantly decreased in a dose-dependent manner after intraperitoneal administration of minaprine 30 min before killing. In rats injected with minaprine 15 mg kg-1 i.p. at different intervals, the decrease in striatal HVA and DOPAC was time-dependent and a concomitant rise in 3-methoxytyramine (3-MT) concentrations was observed. The maximum of these effects was reached 30 min after minaprine. When administered 5 min after a monoamineoxidase (MAO) inhibitor (pargyline, 100 mg kg-1 i.p.) and 30 min before killing, minaprine did not affect pargyline-induced changes in HVA, DOPAC and 3-MT levels. This together with other data suggests that minaprine affects DA metabolism by acting, at least partially, at presynaptic level through in-vivo inhibition of MAO activity.

Animals↗

Idiopathic torsion dystonia associated with lesions of the basal ganglia.

We report two siblings who are suffering from a dystonic syndrome, clinically indistinguishable from idiopathic torsion dystonia (dystonia musculorum deformans) but with cranial computerized tomographic scan findings of basal ganglia lesions, similar to that reported in Wilson's disease. The occurrence of the disorder in the same sibship suggests an autosomal recessive mode of inheritance and may represent another variety of the syndrome of idiopathic torsion dystonia.

Adolescent↗

Effects of systemic and intracerebroventricular domperidone treatment on striatal and hypothalamic dopaminergic neurons.

In this study we compared the effects of systemic administration of haloperidol (HAL), a typical dopaminergic antagonist and of domperidone (DOM), a dopamine (DA) receptor blocker which does not cross the blood brain barrier but has a potency similar to HAL at DA receptors, on hypothalamic and striatal DA system turnover (evaluated by means of HVA and DOPAC levels) and prolactin (PRL) secretion in male rats. In accordance with previous data, we found that HAL (1 mg/kg, i.p.) raised DOPAC and HVA levels whereas DOM (1 mg/kg, i.p.) did not alter DA turnover in striatum. Both DOM and HAL affected the hypothalamic DA system, increasing DOPAC levels in a pattern similar to that observed in PRL secretion. An intracerebroventricular (icv) injection of DOM and HAL (4 micrograms/10 microliters/rat) was then made to investigate its effect on DA turnover in this experimental condition at striatal and hypothalamic level. DOM stimulated DA turnover a little in the striatum though its action was delayed; no effects were seen on HVA and DOPAC concentrations in the hypothalamus at any of the tested times. On the other hand, an equal amount of HAL induced an increase in striatal HVA and DOPAC levels, with no significant effects on hypothalamic DA metabolites. These results show that systematically administered DOM and HAL may affect the hypothalamic tuberoinfundibular DA system, probably acting through PRL release. Furthermore DOM, even when injected icv, shows only weak antidopaminergic action on DA turnover in both central areas.

3,4-Dihydroxyphenylacetic Acid↗

Ovine prolactin administration modifies [3H]spiperone binding to striatal membranes of rabbits.

The binding of [3H]spiperone to striatal membranes from rabbit brain was evaluated in untreated male and female and in female rabbits after treatment with ovine prolactin (1 mg/kg, i.v.) or with saline. Unsubstantial differences were found between male and female striatal [3H]spiperone binding sites, both in affinity and density. Ovine prolactin treatment induced an increased binding site density and a lower affinity than occurred in the female controls. These results appear similar to those obtained after chronic neuroleptic treatment and confirm that prolactin is able to affect the dopaminergic neurotransmission system.

Animals↗

Ergot alkaloids and phosphodiesterase; 'in vitro' activities in several rat brain areas.

The 'in vitro' activity of ergotamine, dihydroergocristine, dihydroergocornine and dihydroergocryptine on the phosphodiesterase system at low and high Km in several rat brain areas was examined. These drugs were found to exert an inhibitory effect in all the areas examined with regard to both systems, and particularly on low substrate concentration phosphodiesterases.

Animals↗

Residual developmental disabilities in children with transient hypertonicity in infancy.

Developmental disabilities occurred in children who manifested transient neurologic abnormalities in early infancy. In an attempt to identify associated problems at an earlier age, the neuromotor and developmental progress of 33 children who had transient hypertonicity during early infancy was analyzed. At 2-3 years of age, various developmental abnormalities were identified in more than two-thirds of these children. Delays in speech and language development and also in fine motor/adaptive and behavioral difficulties were most frequently present. Over time, these problems persisted and other disorders also became apparent. At 5 years of age or older, learning disabilities were frequent and associated with language and perceptual problems. None of the patients had epilepsy; mental retardation was present in only 2 children. Our study demonstrates that children with transient hypertonicity in early infancy are at risk for various developmental problems which can be identified as early as 2 years of age. It also indicates that although their severity lessens over time, these developmental abnormalities tend to persist.

Adolescent↗

Autonomic nervous activity during sleep in middle cerebral artery infarction.

No data are available on the autonomic system during sleep in patients with stroke. The purpose of this study was to determine the influence of acute ischemic stroke on the autonomic cardiovascular system during sleep, and to correlate autonomic activity with the clinical status of patients. Ten patients with ischemic stroke in the middle cerebral artery were studied by means of an all-night polysomnographic recording within the 1st week of the onset of symptoms and at the 3-week follow-up examination. Power spectrum analysis of the heart rate variability was performed using an autoregressive algorithm in 180 consecutive electrocardiographic RR intervals. Spectral power was calculated in 3 main frequency bands: high frequency (HF), 0.15-0.4 Hz; low frequency (LF), 0.04-0.15 Hz; very low frequency (VLF), < 0.04 Hz. The data were compared with those of 10 age-matched controls. A significant increase in VLF (p < 0.0005) and a decrease in HF (p < 0.0002) components were found in ischemic stroke patients. The sympathetic-parasympathetic balance (VLF + LF/HF) was higher in patients than controls (p < 0.005). However, these components changed significantly during sleep, revealing a physiological pattern. These power spectral data were still present at the 3-week follow-up. The 4 patients who developed cardiac arrhythmias showed higher sympathetic-parasympathetic balance than patients without arrhythmias (p < 0.05). These data suggest a sympathetic predominance in patients with acute ischemic stroke during sleep. However, the flexible and dynamic properties of the autonomic nervous system are preserved. Cardiac arrhythmias following stroke may be related to the degree of sympathetic predominance.

Aged↗

Free-floating cyst in the anterior chamber: ultrasound biomicroscopic reports.

PURPOSE: To report a free-floating dislodged pigmented cyst in the anterior chamber and to describe the ultrasound biomicroscopic (UBM) features of the lesion. METHODS: Case report. RESULTS: A 26-year-old man presented with noise in his left eye in the prone position. Slit-lamp examination revealed a small pigmented mass lesion at the 6 o'clock position in the anterior chamber, slowly moving with changing head postures. UBM revealed an unfixed dislodged pigmented cyst with a thin wall and no internal reflectivity, changing its shape from ovoid to circular. Five years later, the anterior segment does not show any modification and the cyst has not changed in size or appearance. CONCLUSIONS: Cysts of the iris pigment epithelium arise in the posterior iris layer. They may be central, midzonal, peripheral, or dislodged. Dislodged cysts may be repositioned and fixed or free-floating in the vitreous or in the anterior chamber. Surgical removal must be considered only for a rapid enlargement or significant reduction in endothelial cell count. UBM can distinguish solid from cystic lesions, giving detailed information on internal structure, reflectivity, shape, and thickness.

Adult↗

Photorefractive keratectomy in high myopic defects with or without intraoperative mitomycin C: 1-year results.

PURPOSE: To study the results of the prophylactic use of mitomycin C (MMC) to reduce haze formation and refractive regression after excimer laser photorefractive keratectomy (PRK) for high myopic defects (>5 diopters). METHODS: Prospective, consecutive, observational study. A total of 124 eyes of 62 patients were divided into two groups of 31 patients, 62 eyes each (Groups A and B). Only Group A was treated with MMC 0.02%. The data of the two groups of eyes, related to the best-corrected visual acuity (BCVA), to the difference of refraction pre- and post-treatment, and to the corneal haze, were analyzed through combined permutation tests by using the NPC Test software . RESULTS: BCVA of Group A, 1 year after treatment, was better than that of the control Group B (one-sided p value = 0.013): Group A - 3 eyes (4.8%) had a loss of a decimal fraction and no eyes > 1; Group B - 13 eyes (20.9%) had a loss of a decimal fraction and 1 eye (1.6%) of 2. There was a smaller difference between attempted and achieved SE correction in Group A with respect to Group B (one-sided p value = 0.068): Group A - 43 eyes (69.3%) within +/- 0.50 D; Group B - 31 eyes (50%) within +/- 0.50 D. there was a smaller incidence of corneal haze in the group for which MMC was used (one-sided p value = 0.005). CONCLUSIONS: In this study, the application of MMC 0.02% solution immediately after PRK produced lower haze rates and had better predictability and improved efficacy 1 year after treatment.

Adult↗